Subcutaneous Administration

CHAPTER 1: INTRODUCTION

ANNOUNCER:

INDICATION AND USAGE

UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone.

ANNOUNCER:

This video is intended for healthcare professionals and provides instructions for use of UZEDY (risperidone) subcutaneous injection with a prefilled syringe.

Hi, my name is Matt, and I’m a psychiatric nurse. Today, I’m going to guide you through the administration process for UZEDY. UZEDY comes in a prefilled syringe for subcutaneous injection. There are important steps in this video that must be performed to ensure complete dosing. After watching this demonstration, please refer to the Instructions for Use within the full Prescribing Information before you administer UZEDY for the first time.

CHAPTER 2: PREPARATION

ANNOUNCER:

First, let’s go over the preparation steps for injection.

UZEDY must be brought to room temperature before use, so be sure to remove the injection kit from the refrigerator at least 30 minutes before the scheduled injection appointment.

Remove the contents from the kit.

Ensure the product in the syringe is white to off-white in color, opaque, and free from non-white particulate matter. You also want to verify the label information, including the correct product name, the appropriate dose, and the date of expiration.

Ensure that the kit contains the correct needle size, which is 21-gauge by 5/8 inches. Put gloves on before peeling back the paper tab of the needle pouch to expose the safety needle hub.

Administering UZEDY may be different from other injectable antipsychotics you have experience with because it is viscous. It may have a lower injection volume, and it is ONLY for injection into subcutaneous tissue.

CHAPTER 3: INJECTION

ANNOUNCER:

This chapter addresses the steps to prepare the syringe and injection site and explains how to administer UZEDY.

You can remember these steps with the phrase, “Whip and inspect before you inject.”

This next step is very important. Because UZEDY is viscous, you need to whip the product with a downward motion to move the bubble to the cap of the syringe to ensure your patient receives a complete dose.

With gloves on, hold the syringe by the white collar.

Next, whip the product in a forceful downward motion 3 times.

Inspect the syringe to make sure the small air bubble is at the top near the cap. This helps to prevent any product loss within the tip cap. If the bubble is not at the top of the cap, repeat the whipping motion until it is there.

To attach the needle to the syringe, hold the syringe vertically by the white collar; then bend and snap off the cap. Keeping the syringe in this position, push the green hub of the safety needle inside the white collar; then twist the needle until it’s secure.

The syringe and needle are ready for injection.

Some patients with schizophrenia have a fear of pain or discomfort with receiving an injection, so be sure to answer any questions they may have, especially if this is their first time receiving a UZEDY injection.

With UZEDY, you and your patient can choose a subcutaneous injection site from the stomach area, around the belly button, or back and outer area of the upper arms. This patient has chosen to receive their injection in the arm.

Once you and your patient have identified the injection site, use an alcohol wipe to clean it; then let it dry completely.

Pull the needle sheath away from the green hub to expose the needle.

Remember, UZEDY is for subcutaneous injection only.

Pinch at least 1 inch of the area of clean skin with your free hand.

Insert the needle into the pinched skin to achieve a subcutaneous injection. Do not apply pressure to the plunger rod just yet.

Once the needle is in the subcutaneous tissue, you can release the pinched skin.

Push on the end of the plunger rod using a slow, firm, and steady push until the entire dose is delivered.

Because UZEDY is viscous, you may experience some resistance during dose delivery, but do not use excessive force in an attempt for faster delivery.

Wait 2 to 3 seconds after the entire dose is delivered before slowly pulling the needle out of the skin at the same angle as the insertion.

CHAPTER 4: POST INJECTION

ANNOUNCER:

Now that you have injected UZEDY, it’s time to safely dispose of the needle.

To activate the clear safety shield, lock the safety needle shield using a hard surface, or, like me, using your finger and thumb. You will hear an audible “click” when you have locked the needle safety sheath.

Dispose of the syringe and needle safely in a suitable sharps container. You do not need to disconnect the needle from the syringe.

The injection is now complete.

Thank you for watching this video, which outlined the important administration instructions for UZEDY, a subcutaneous, long-acting injectable for patients with schizophrenia.

Please stay tuned for additional Important Safety Information for UZEDY.

IMPORTANT SAFETY INFORMATION (CONTINUED)

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the 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 TD is unknown.

The risk of developing TD and the likelihood that it will become irreversible are believed to 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. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.

Hyperprolactinemia: As with other drugs that antagonize dopamine D ₂ receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.

Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication.

Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm ³) and follow their WBC until recovery.

Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely.

Seizures During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration.

Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention.

Body temperature regulation. Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions.

ADVERSE REACTIONS

The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.

The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule.

DRUG INTERACTIONS

• Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone.
• Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration.
• Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.
• UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.
• UZEDY may antagonize the pharmacologic effects of dopamine agonists.
• Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS)

USE IN SPECIFIC POPULATIONS

Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS.

Fertility: UZEDY may cause a reversible reduction in fertility in females.

Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients.

Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY.

Patients with Parkinson’s disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS.

Please see the full Prescribing Information for UZEDY, including Boxed WARNING.