complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/μL in absence of other causative factors, and continue monitoring WBC count until recovery May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Use caution in patients at risk of pneumonia; esophageal dysmotility and aspiration reported with antipsychotic use May cause extrapyramidal symptoms including acute dystonic reactions, akathisia, pseudoparkinsonism, and tardive dyskinesia Intraoperative floppy iris syndrome reported in patients receiving risperidone therapy Monitor for fever, mental status changes, muscle rigidity and or autonomic instability; neuroleptic malignant syndrome (NMS) associated with risperidone use; if NMS suspected, discontinue therapy immediately and provide symptomatic treatment and monitoring Use with caution in children <15 kg Cases of priapism reported with therapy Prolactin elevations occur and persist during chronic administration; risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents Use caution when operating heavy machinery FDA warning regarding off-label use for dementia in elderly Seizures observed during premarketing studies of risperidone in adult patients with schizophrenia Esophageal dysmotility and aspiration have been associated with antipsychotic use Disruption of body temperature regulation has been attributed to antipsychotic agents Tardive dyskinesia A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs; although prevalence appears to be highest among elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome; whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown Risk of developing tardive dyskinesia and likelihood that it will become irreversible increase with the duration of treatment and the cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low doses. It may also occur after discontinuation of treatment Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is discontinued; antipsychotic treatment, itself, however, may suppress (or partially suppress) signs and symptoms of the syndrome, possibly masking the underlying process Therapy should be prescribed in a manner that is most likely to minimize occurrence of tardive dyskinesia; chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness known to respond to antipsychotic drugs, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate In patients who do require chronic treatment, use lowest dose and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued treatment; If signs and symptoms of tardive dyskinesia appear in a patient receiving therapy, consider discontinuing drug; however, some patients may require treatment with the drug despite the presence of the syndrome Orthostatic hypotension May induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during initial dose-titration period, probably reflecting its alpha-adrenergic antagonistic properties risk of orthostatic hypotension and syncope may be minimized by limiting the initial dose to 2 mg total (either once daily or 1 mg twice daily) in normal adults and 0.5 mg twice daily in the elderly and patients with renal or hepatic impairment Risk of orthostatic hypotension and syncope may be minimized by limiting initial dose to 2 mg total (either once daily or 1 mg twice daily) in normal adults and 0.5 mg twice daily in the elderly and patients with renal or hepatic impairment Consider monitoring orthostatic vital signs in patients at risk; consider dose reduction if hypotension occurs Use caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions that would predispose patients to hypotension, eg, dehydration and hypovolemia, and in the elderly and patients with renal or hepatic impairment Consider monitoring for orthostatic vital signs if hypotension occurs; clinically significant hypotension observed with concomitant use of drug and antihypertensive medication Metabolic changes Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk (eg, hyperglycemia, dyslipidemia, and body weight gain) In some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone Pregnancy Neonates exposed to antipsychotic drugs during third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery Available data from published epidemiologic studies of pregnant females exposed to risperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes There are risks to the mother associated with untreated schizophrenia or bipolar disorder and with exposure to antipsychotics Risperidone has been detected in plasma in adult subjects up to 6 weeks after a single dose Clinical significance administered before or during pregnancy is unknown Pregnancy exposure registry Registry monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy Register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961- 2388 or online at http://womensmentalhealth.org/clinicaland-research-programs/pregnancyregistry/ Infertility Based on the pharmacologic action of risperidone, treatment may result in an increase in serum prolactin levels, which may lead to reversible reduction in fertility in females of reproductive potential Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth It is not known if this is a direct result of the illness or other comorbid factors Fetal/neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder reported in neonates who were exposed to antipsychotic drugs, including risperidone, during the third trimester of pregnancy; symptoms varied Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately Lactation Limited data are available the presence of risperidone and its metabolite, 9- hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3 and 4.7% of the maternal weight-adjusted dosage Reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Has high affinity for serotonin type 2 (5-HT2) receptors; binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2 receptors; antagonizes alpha1-adrenergic, alpha2-adrenergic, and histaminergic receptors; has moderate affinity for serotonin type 1 (5-HT1C, 5-HT1D, 5-HT1A) receptors; has weak affinity for dopamine D1 receptors; has no affinity for muscarinic, beta1-adrenergic, and beta2-adrenergic receptors Absorption Peak plasma concentration: 6.33-10.9 ng/mL (risperidone, 9-hydroxyrisperidone) AUC: 2262-3891 ng·hr/mL Bioavailability: 70% Peak plasma time PO: 3 hr (extensive metabolizers); 17 hr (poor metabolizers) IM (Rykindo): 14 days (risperidone); 17 days (9-hydroxyrisperidone) Steady state reached at IM: 4-6 weeks (Risperdal Consta): 2-3 weeks (Rykindo) SC: 4-6 hr Distribution Risperidone once absorbed is rapidly distributed Vd Risperdal Consta: 1-2 L/kg Protein bound Risperidone: ~90% 9-hydroxyrisperidone (major metabolite): 77% Metabolism Extensively metabolized by liver Metabolite: 9-hydroxyrisperidone (paliperidone) Elimination Half-life IM: 3-6 days PO: Extensive metabolizers, 3 hr (parent and metabolite combined); poor metabolizers, 20 hr (parent and metabolite combined); prolonged in renal impairment; free fraction increase in hepatic disease Excretion Urine (70%) Feces (14%) Oral Administration Oral solution Administer directly from the calibrated pipette, or can be mixed with a beverage prior to administration Compatible in the following beverages: Water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea Orally disintegrating tablets Do not open the blister until ready to administer For single tablet removal, separate one of the four blister units by tearing apart at the perforations Bend the corner where indicated Peel back foil to expose the tablet DO NOT push the tablet through the foil because this could damage the tablet The child-resistant pouch should be torn open at the notch to access the blister; do not open the blister until ready to administer Peel back foil from the side to expose the tablet DO NOT push the tablet through the foil, because this could damage the tablet Using dry hands, remove the tablet from the blister unit and immediately place the entire oral disintegration on the tongue; consumed immediately, as the tablet cannot be stored once removed from the blister unit Disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid; patients should not attempt to split or to chew the tablet SC Preparation Perseris Remove kit from refrigerator and allow to sit at room temperature (20-25ºC [68-77ºF]) for at least 15 minutes Visually inspect for particulate matter and discoloration before administering Hold powder syringe upright tap barrel of the syringe to unpack the powder Remove caps from both powder syringe and diluent syringe Connect both syringes; do not over tighten Keep your fingers off the plunger to avoid drug spillage Failure to fully mix the product could result in incorrect dosage Premixing Transfer contents of liquid syringe into powder syringe Gently push powder syringe plunger until you feel resistance (to wet powder and avoid compacting) Repeat this gentle back-and-forth process for 5 cycles Complete mixing Continue mixing syringes for an additional 55 cycles; mixing can be more vigorous than when premixing When fully mixed, product should be a cloudy suspension that is uniform in color; varies between white to yellow-green in color If any clear areas appear in mixture, continue to mix until color is evenly distributed SC Preparation (Uzedy) Remove kit from refrigerator and allow to sit at room temperature (20-25C [68-77F]) for at least 30 minutes Uzedy is a solid at refrigerated temperatures and must reach room temperature before administration; do not warm any other way and keep protected from light Ensure drug in syringe is white to off-white, opaque in color, and free from non-white particulate matter See complete instructions in prescribing information on how to prepare syringe to move the bubble to the cap in ensure complete dosage SC Administration For SC injection only; do not administer by any other route Administer SC in abdomen or back of upper arm To be administered by a healthcare professional only Choose an injection site with adequate SC tissue that has no skin conditions (eg, nodules, lesions, excessive pigment); recommended patient be in the supine position; rotate injection sites (refer to prescribing information) Only prepare medication when you are ready to administer the dose As a universal precaution, always wear gloves IM preparation Remove dose pack from refrigerator; allow to sit at room temperature at least 30 minutes before reconstituting; do not warm any other way Remove vial cap; connect vial adapter Keep vial vertical to prevent leakage Hold base of vial and pull up on the sterile blister to remove; do not shake; do not touch exposed luer opening on vial adapter; this will result in contamination Remove cap from liquid cap; connect liquid syringe to the vial adapter Inject entire amount of diluent from syringe to vial Keep syringe plunger down; shake vigorously for at least 30 sec (Rykindo) and at least 10-20 sec for (Risperdal Consta) When properly mixed, suspension appears uniform, thick, and milky in color Risperdal Consta has microspheres visible in the liquid Immediately invert vial completely, slowly pull plunger rod down to withdraw entire contents from vial into syringe Hold Luer-lock adapter on syringe and unscrew from vial adapter; tear section of vial label at the perforation; apply detached label