Risperdal Consta

• Tablets: 0.25, 0.5, 1, 2, 3, and 4 mg.
• Oral solution: 1 mg/mL.
• Orally disintegrating tablets: 0.25, 0.5, 1, 2, 3, and 4 mg.
• Powder for injection: 12.5, 25, 37.5, and 50 mg.

Tablets should be kept at room temperature, 15 C to 25 C (59 F to 77 F).

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Risperdal Consta there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed. Risperdal Consta can cross into human breast milk. It may harm your baby.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• If you have an allergy to risperidone or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take Risperdal Consta or for 3 months after your last dose.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• If you are planning to harm yourself or the want to harm yourself gets worse.
• Very bad dizziness or passing out.
• Change in how you act.
• Mood changes.
• Shakiness, trouble moving around, or stiffness.
• Not able to pass urine or change in how much urine is passed.
• Trouble swallowing or speaking.
• Not able to focus.
• Seizures.
• Change in eyesight.
• Shortness of breath.
• Drooling.
• Enlarged breasts.
• Change in sex ability.
• Nipple discharge.
• For women, no period.
• Call your doctor right away if you have a painful erection (hard penis) or an erection that lasts for longer than 4 hours. This may happen even when you are not having sex. If this is not treated right away, it may lead to lasting sex problems and you may not be able to have sex.
• A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.
• Very bad irritation where the shot was given.

• If you need to store Risperdal Consta at home, talk with your doctor, nurse, or pharmacist about how to store it.

Schizophrenia

The effectiveness of Risperdal Consta® in the treatment of schizophrenia was established, in part, on the basis of extrapolation from the established effectiveness of the oral formulation of risperidone. In addition, the effectiveness of Risperdal Consta® in the treatment of schizophrenia was established in a 12-week, placebo-controlled trial in adult psychotic inpatients and outpatients who met the DSM-IV criteria for schizophrenia.

Efficacy data were obtained from 400 patients with schizophrenia who were randomized to receive injections of 25 mg, 50 mg, or 75 mg Risperdal Consta® or placebo every 2 weeks. During a 1-week run-in period, patients were discontinued from other antipsychotics and were titrated to a dose of 4 mg oral RISPERDAL®. Patients who received Risperdal Consta® were given doses of oral RISPERDAL® (2 mg for patients in the 25-mg group, 4 mg for patients in the 50-mg group, and 6 mg for patients in the 75-mg group) for the 3 weeks after the first injection to provide therapeutic plasma concentrations until the main release phase of risperidone from the injection site had begun. Patients who received placebo injections were given placebo tablets.

Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS), a validated, multi-item inventory, composed of five subscales to evaluate positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression.

The primary efficacy variable in this trial was change from baseline to endpoint in the total PANSS score. The mean total PANSS score at baseline for schizophrenic patients in this study was 81.5.

Total PANSS scores showed significant improvement in the change from baseline to endpoint in schizophrenic patients treated with each dose of Risperdal Consta® (25 mg, 50 mg, or 75 mg) compared with patients treated with placebo. While there were no statistically significant differences between the treatment effects for the three dose groups, the effect size for the 75 mg dose group was actually numerically less than that observed for the 50 mg dose group.

Subgroup analyses did not indicate any differences in treatment outcome as a function of age, race, or gender.

Bipolar Disorder - Monotherapy

The effectiveness of Risperdal Consta® for the maintenance treatment of Bipolar I Disorder was established in a multicenter, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I, who were stable on medications or experiencing an acute manic or mixed episode.

A total of 501 patients were treated during a 26-week open-label period with Risperdal Consta® (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg; in patients not tolerating the 25 mg dose, the dose could be reduced to 12.5 mg). In the open-label phase, 303 (60%) patients were judged to be stable and were randomized to double-blind treatment with either the same dose of Risperdal Consta® or placebo and monitored for relapse. The primary endpoint was time to relapse to any mood episode (depression, mania, hypomania, or mixed).

Time to relapse was delayed in patients receiving Risperdal Consta® monotherapy as compared to placebo. The majority of relapses were due to manic rather than depressive symptoms. Based on their bipolar disorder history, subjects entering this study had had, on average, more manic episodes than depressive episodes.

Bipolar Disorder - Adjunctive Therapy

The effectiveness of Risperdal Consta® as an adjunct to treatment with lithium or valproate for the maintenance treatment of Bipolar Disorder was established in a multi-center, randomized, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who experienced at least 4 episodes of mood disorder requiring psychiatric/clinical intervention in the previous 12 months, including at least 2 episodes in the 6 months prior to the start of the study.

A total of 240 patients were treated during a 16-week open-label period with Risperdal Consta® (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg), as adjunctive therapy in addition to continuing their treatment as usual for their bipolar disorder, which consisted of mood stabilizers (primarily lithium and valproate), antidepressants, and/or anxiolytics. All oral antipsychotics were discontinued after the first three weeks of the initial Risperdal Consta® injection. In the open-label phase, 124 (51.7%) were judged to be stable for at least the last 4 weeks and were randomized to double-blind treatment with either the same dose of Risperdal Consta® or placebo in addition to continuing their treatment as usual and monitored for relapse during a 52-week period. The primary endpoint was time to relapse to any new mood episode (depression, mania, hypomania, or mixed).

Time to relapse was delayed in patients receiving adjunctive therapy with Risperdal Consta® as compared to placebo. The relapse types were about half depressive and half manic or mixed episodes.

Physicians are advised to discuss the following issues with patients for whom they prescribe Risperdal Consta®.

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension and instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position) [see Warnings and Precautions (5.7)].

Interference with Cognitive and Motor Performance

Because Risperdal Consta® has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that treatment with Risperdal Consta® does not affect them adversely [see Warnings and Precautions (5.10)].

Pregnancy

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy and for at least 12 weeks after the last injection of Risperdal Consta® [see Use in Specific Populations (8.1)].

Nursing

Patients should be advised not to breast-feed an infant during treatment and for at least 12 weeks after the last injection of Risperdal Consta® [see Use in Specific Populations (8.3)].

Concomitant Medication

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)].

Alcohol

Patients should be advised to avoid alcohol during treatment with Risperdal Consta® [see Drug Interactions (7.1)].

Product of Ireland

Risperidone active ingredient is manufactured by:
Janssen Pharmaceutical
Wallingstown, Little Island, County Cork, Ireland

Microspheres are manufactured by:
Alkermes, Inc.
Wilmington, Ohio

Diluent is manufactured by:
Vetter Pharma Fertigung GmbH & Co. KG
Langenargen, Germany

or

Cilag AG
Schaffhausen, Switzerland

Risperdal Consta® is manufactured for:
Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560

© 2007 Janssen Pharmaceutical Companies

25 mg
Dose Pack

Store Package
in Refrigerator
(see bottom panel for
storage conditions)

Rx only
Single use only

NDC 50458-306-11

RisperdalCONSTA®
risperiDONE Long-Acting Injection

DOSE PACK CONTENTS:

• One 25 mg vial of risperidone extended-release microspheres for injection
• One pre-filled syringe containing 2 mL of diluent
• One West-Medimop Vial Adapter®
• One 21-gauge UTW 1" Terumo SurGuard® 3 safety needle for deltoid injection
• One 20-gauge TW 2" Terumo SurGuard® 3 safety needle for gluteal injection

Do not substitute any components of the dose pack.

For deltoid or gluteal intramuscular injection only
Each injection should be administered by a healthcare professional.

PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE.

Risperdal Consta is injected into a muscle. A healthcare provider will give you this injection.

Risperdal Consta is usually given once every 2 weeks. You may also need to take risperidone by mouth in pill or liquid form during the first 3 weeks of your treatment with the injections. Follow your doctor's instructions.

Call your doctor for instructions if you miss an appointment for your Risperdal Consta injection.

Get emergency medical help if you have any signs of an allergic reaction to Risperdal Consta: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);

• breast swelling or tenderness (in men or women), nipple discharge, impotence, lack of interest in sex, missed menstrual periods;

• severe nervous system reaction - very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;

• low white blood cells - sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing, skin sores, cold or flu symptoms, cough, trouble breathing;

• low levels of platelets in your blood - easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• high blood sugar - increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• penis erection that is painful or lasts 4 hours or longer.

Common Risperdal Consta side effects may include:

• headache;

• dizziness, drowsiness, tired feeling;

• feeling hot or cold;

• tremors, twitching or uncontrollable muscle movements;

• agitation, anxiety, restless feeling;

• depressed mood;

• dry mouth, upset stomach, constipation;

• weight gain; or

• pain in your arms or legs.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.