Indicated for:

Schizophrenia:

• The treatment of schizophrenia.

Bipolar Disorder:

• As monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. RISPERDAL CONSTA is not approved for the treatment of patients with dementia-related psychosis.

Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73-97) in trials of oral risperidone in elderly patients with dementia-related psychosis.

For patients who have never taken oral RISPERDAL, it is recommended to establish tolerability with oral RISPERDAL prior to initiating treatment with RISPERDAL CONSTA.

RISPERDAL CONSTA should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection.

A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentrations or in patients who have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Oral RISPERDAL (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA and continued for 3 weeks (and then discontinued) to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site.

Upward dose adjustment should not be made more frequently than every 4 weeks. The clinical effects of this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose.

Do not combine two different dose strengths of RISPERDAL CONSTA in a single administration.

Patients with renal or hepatic impairment should be treated with titrated doses of oral RISPERDAL prior to initiating treatment with RISPERDAL CONSTA.

Previous antipsychotics should be continued for 3 weeks after the first injection of RISPERDAL CONSTA to ensure that therapeutic concentrations are maintained until the main release phase of risperidone from the injection site has begun.

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs.

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs.

Tardive dyskinesia, 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. The risk of developing tardive dyskinesia and the 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.

RISPERDAL CONSTA should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients: (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the lowest dose and the shortest duration of treatment producing a satisfactory clinical response.

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.

Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics including RISPERDAL. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics, including RISPERDAL, should be monitored regularly for worsening of glucose control.

As with other drugs that antagonize dopamine D2 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.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects

RISPERDAL CONSTA may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period with oral risperidone, probably reflecting its alpha-adrenergic antagonistic properties.

RISPERDAL CONSTA should be used with particular caution in (1) patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension, e.g., dehydration and hypovolemia, and (2) in the elderly and patients with renal or hepatic impairment.

Somnolence, postural hypotension, motor and sensory instability have been reported with the use of antipsychotics, including RISPERDAL CONSTA, which may lead to falls and, consequently, fractures or other fall-related injuries.

In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including RISPERDAL CONSTA. Agranulocytosis has also been reported.

RISPERDAL CONSTA should be used cautiously in patients with a history of seizures.

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. RISPERDAL CONSTA and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

Priapism has been reported during postmarketing surveillance.

Disruption of body temperature regulation has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral RISPERDAL or RISPERDAL CONSTA use.

The interactions of RISPERDAL CONSTA with co-administration of other drugs have not been systematically evaluated in human subjects. Drug interactions are based primarily on experience with oral RISPERDAL.

Co-administration of carbamazepine and other CYP3A4 enzyme inducers (e.g., phenytoin, rifampin, phenobarbital) with risperidone would be expected to cause decreases in the plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone combined, which could lead to decreased efficacy of RISPERDAL CONSTA treatment.

At the initiation of therapy with carbamazepine or other known CYP3A4 hepatic enzyme inducers, patients should be closely monitored during the first 4-8 weeks, since the dose of RISPERDAL CONSTA may need to be adjusted. A dose increase, or additional oral RISPERDAL, may need to be considered.

On discontinuation of carbamazepine or other CYP3A4 hepatic enzyme inducers, the dosage of RISPERDAL CONSTA should be re-evaluated and, if necessary, decreased.

Patients may be placed on a lower dose of RISPERDAL CONSTA between 2 to 4 weeks before the planned discontinuation of carbamazepine or other CYP3A4 inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone.

Fluoxetine and paroxetine, CYP2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5-2.8 fold and 3-9 fold respectively.

When initiation of fluoxetine or paroxetine is considered, patients may be placed on a lower dose of RISPERDAL CONSTA between 2 to 4 weeks before the planned start of fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of risperidone.

When RISPERDAL CONSTA is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered.

Given the primary CNS effects of risperidone, caution should be used when RISPERDAL CONSTA is administered in combination with other centrally-acting drugs or alcohol.

RISPERDAL CONSTA may antagonize the effects of levodopa and dopamine agonists.

Cimetidine and ranitidine increased the bioavailability of oral risperidone by 64% and 26%, respectively.

Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.

Treatment with RISPERDAL CONSTA may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential.

Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

Animal studies: cleft palate, stillbirths and decreased birth weight.

Limited data from published literature reports 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. There are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone. Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of RISPERDAL CONSTA.

GoToSource

• Use in patients under 18 years of age. GoToSource

• Attention-deficit hyperactivity disorder, anxiety, dementia, depression, eating disorders, insomnia, obsessive-compulsive disorder, personality disorder, post-traumatic stress disorder, substance use and dependence disorders and tourette’s syndrome. GoToSource

• Autism spectrum disorders and dementia. GoToSource

Exacerbation of working memory impairments. GoToSource

Sedation, sexual dysfunction, postural hypotension (drop in blood pressure due to change in body position), cardiac arrhythmia and sudden cardiac death. GoToSource

Pathological gambling, hypersexuality and compulsive eating and shopping. GoToSource

Tardive dyskinesia (involuntary movements). GoToSource

Severe arterial hypertension resulting in posterior reversible cerebral edema syndrome. GoToSource 

Acute eosinophilic pneumonia (eosinophil, a type of white blood cell, accumulates in the lung). GoToSource

A 3-fold increased risk for type 2 diabetes. GoToSource

Weight gain. GoToSource

Priapism (persistent and painful erection). GoToSource

Deep vein thrombosis (blood clot forms in one or more of the deep veins in body) and pulmonary embolism (blockage in one of the pulmonary arteries in lungs). GoToSource

Iron depletion and deficiency. GoToSource

Activation of mania. GoToSource

Restless legs syndrome. GoToSource

Rabbit syndrome (rhythmic motion of the mouth and lips). GoToSource

Use in patients with dementia increases risk of cerebrovascular adverse events such as stroke and transient ischemic attacks, including fatalities. GoToSource

Increased levels of prolactin causing gynecomastia (enlargement of male breast tissue) and galactorrhea (milky nipple discharge). GoToSource

Neuroleptic malignant syndrome (life-threatening neurological disorder). GoToSource

Pancreatitis (inflammation of pancreas). GoToSource

Pituitary tumors. GoToSource

Leukopenia (decreased number of white blood cells). GoToSource

Neutropenia (low level of neutrophils a type of white blood cell). GoToSource

Agranulocytosis (lowered white blood cell count). GoToSource

Seizures. GoToSource

Dysphagia (difficulty swallowing). GoToSource

Lawsuits filed for gynecomastia, diabetes, bone loss, sexual dysfunction, pituitary tumors, tardive dyskinesia, neuroleptic malignant syndrome, heart attacks, pancreatitis and death.