RiteMed Risperidone Special Precautions

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. Risperidone and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
Suicide: The possibility of suicide or attempted suicide is inherent in psychosis and bipolar mania, and thus, close supervision and appropriate clinical management of high-risk patients should accompany drug therapy.
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex that has been reported in association with antipsychotic drugs, including risperidone.
Clinical manifestations of NMS are hyperthermia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular blood pressure, tachycardia, cardiac arrhythmias, and diaphoresis). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.
The management of NMS should include: immediate discontinuation of all antipsychotic drugs including risperidone, and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrence of NMS has been reported.
Tardive Dyskinesia (TD): A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with conventional antipsychotic drugs. Although TD appears to be most prevalent in the elderly, particularly elderly females, it is impossible to predict at the onset of treatment which patients are likely to develop TD. It has been suggested that the occurrence of parkinsonian side effects is a predictor for the development of TD. In clinical studies, the observed incidence of drug-induced parkinsonism was lower with risperidone than with haloperidol. The risk of developing TD may be less with risperidone. In longer-term clinical studies, risperidone was associated with a lower incidence of treatment-emergent dyskinesia compared to haloperidol.
The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although less commonly, after relatively brief periods of treatment at low doses. There is known treatment for established cases of TD. The syndrome may remit, partially or completely, if antipsychotic drug treatment is withdrawn. However, antipsychotic drug treatment itself may suppress the signs and symptoms of TD, thereby masking the underlying process. The effect of symptom suppression upon the long-term course of TD is unknown.
In view of these considerations, risperidone should be prescribed in a manner that is most likely to minimize the risk of TD. As with any antipsychotic drug, risperidone should be reserved for patients who appear to be obtaining substantial benefit from the drug. In such patients, the smallest dose and the shorted duration of treatment should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of TD develop during treatment with risperidone, withdrawal of the drug should be considered. However, some patients may require treatment with risperidone despite the presence of the syndrome.
Seizures: Antipsychotic drugs are known to lower the seizure threshold. In clinical trials, seizures have occurred in a few patients treated with risperidone. Therefore, caution should be used in administering risperidone to patients having a history of seizures or other predisposing factors.
Akathisia: The presentation of akathisia may be variable and comprises subjective complaints of restlessness and an overwhelming urge to move and either distress or motor phenomena such as pacing, swinging of the legs while seated, rocking from foot to foot, or both. Particular attention should be paid to the monitoring for such symptoms and signs as, left untreated, akathisia is associated with poor compliance and an increased risk of relapse.
Use in Patients with Parkinson's Disease or Dementia with Lewy Bodies (DLB): Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including risperidone, to patients with Parkinson's Disease or DLB since both groups may be at increased risk of NMS as well as having an increased sensitivity to antipsychotic medications. Manifestation of this increased sensitivity can include confusion, obtundation, and postural instability with frequent falls, in addition to extrapyramidal symptoms.
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.
Hyperglycemia and Diabetes Mellitus: As with some other antipsychotics, hyperglycemia, diabetes mellitus and exacerbation of pre-existing diabetes, in some cases serious and associated with ketoacidosis or hyperosmolar coma or death, have been reported during the use of risperidone. Diabetic ketoacidosis has occurred in patients treated with antipsychotics with no reported history of hyperglycemia. Appropriate clinical monitoring of patients treated with antipsychotics is advisable in accordance with utilized antipsychotic guidelines.
Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.
Any patient treated with atypical antipsychotics, including risperidone, should be monitored for symptoms of hyperglycemia and diabetes mellitus including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia and diabetes mellitus during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control.
Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
When treating pediatric patients with risperidone for any indication, weight gain should be assessed against the expected with normal growth.
Hyperprolactinemia: 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.
Since tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, risperidone should only be administered to patients with previously detected breast cancer if the benefits outweigh the potential risks. Caution should also be exercised when considering risperidone treatment in patients with pituitary tumors. Possible manifestations associated with elevated prolactin levels are amenorrhea, galactorrhea, and menorrhagia. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone mineral density in both female and male subjects.
Orthostatic Hypotension: Risperidone has been observed to cause orthostatic hypotension and tachycardia, particularly during the initial dose titration period and the first few weeks of treatment, during clinical trials. Rare cases of syncope, cardiac arrhythmias and first degree AV-block have been reported. Clinically significant hypotension has also been observed post-marketing with concomitant use of risperidone and antihypertensive treatment. The likelihood of excessive hypotension or syncope can be minimized by limiting the initial dose of the drug to 1 to 2 mg per day, once or twice daily, in adult patients and to 0.25 to 0.5 mg twice per day in special patient populations, and by increasing the dose slowly. A dose reduction should be considered if hypotension occurs.
Risperidone should be used with caution in patients with cardiovascular diseases (e.g., heart failure, history of myocardial infarction or ischemia, cerebrovascular disease, conduction abnormalities) and other conditions such as dehydration and hypovolemia. Special care should be taken to avoid hypotension in patients with a history of cerebrovascular insufficiency or ischemic heart disease, and in patients taking medications to lower blood pressure. Monitoring of orthostatic vital signs should be considered in all such patients.
QT interval: As with other antipsychotics, caution should be exercised when risperidone is prescribed in patients with a history of cardiac arrhythmias, in patients with congenital long QT syndrome, and in concomitant use with drugs known to prolong the QT interval.
Leukopenia, Neutropenia, and Agranulocytosis Class Effect: In clinical trial and/or post-marketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including risperidone. Granulocytopenia and agranulocytosis have also been reported.
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should be monitored during the first few months of therapy and discontinuation of risperidone should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur.
Patients with severe neutropenia (absolute neutrophil count <1 x 10⁹/L) should discontinue risperidone and have their WBC followed until recovery.
Venous thromboembolism (VTE): VTE, including fatal pulmonary embolism, has been reported with antipsychotic drugs, including risperidone, in case reports and/or observational studies. When prescribing risperidone all potential risk factors for VTE should be identified and preventive measures undertaken.
Priapism: Drugs with α-adrenergic blocking effects have been reported to induce priapism. Priapism has been reported with risperidone during post-marketing surveillance. This adverse reaction, as with other psychotropic drugs, did not appear to be dose dependent and did not correlate with the duration of treatment.
Body temperature regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic drugs. Appropriate care is advised when prescribing risperidone for patients who will be experiencing conditions which may contribute to an elevation or reduction of core temperature, e.g., exercising strenuously, exposure to extreme heat or cold, receiving concomitant drug with anticholinergic activity, or being subject to dehydration.
Antiemetic effect: Consistent with its dopamine antagonistic effects, risperidone may have an antiemetic effect. Such an effect may mask signs of toxicity due to overdosage with other drugs, or may mask symptoms of disease such as brain tumor, or intestinal obstruction or Reye's syndrome.
Intraoperative Floppy Iris Syndrome (IFIS): IFIS has been observed during cataract surgery in patients treated with medicines with α₁-adrenergic antagonist effect, including risperidone.
This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs and potential prolapse of the iris toward the phacoemulsification incisions. IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with α₁-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping α₁ blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.
Use in Patients with Concomitant Illness: As clinical experience is limited, risperidone should be used with caution in patients with dehydration, hypokalemia, and hypovolemia.
Effects on Ability to Drive and Use Machine: Since risperidone may cause somnolence, patients should be cautioned against driving a car or operating hazardous machinery until they are reasonably certain that risperidone does not affect them adversely.
Use in Children: Before risperidone is prescribed to a child or adolescent with conduct disorder, they should be fully assessed for physical and social causes of the aggressive behavior such as pain or inappropriate environmental demands.
The sedative effect of risperidone should be closely monitored in this population because of possible consequences on learning ability. A change in the time of administration of risperidone could improve the impact of the sedation on attention faculties of children and adolescents.
Risperidone treatment for up to three years showed no adverse effects on growth and sexual maturation. No differences were observed between risperidone and placebo groups in measurements of sexual maturation, using the Tanner scale, and no adverse events suggestive of delayed pubertal maturation were reported. The mean change in height after one year of treatment with risperidone was within the expected growth range in this population.
Weight gain has been observed with atypical antipsychotic use in pediatric and adolescent patient populations. Independent of any drug-specific effects, weight gain can be associated with adverse changes in other metabolic parameters (e.g., glucose and lipid metabolism). Abnormal childhood weight and metabolic status can have adverse effects on cardiovascular outcomes in adulthood. Weight gain and adverse effects on other metabolic parameters associated with typical antipsychotics can be more frequent or more severe in pediatric and adolescent patients than in the adult patients.
During treatment with risperidone, regular examination for extrapyramidal symptoms and other movement disorders should also be conducted.
Safety and effectiveness of risperidone in children less than 13 years old with schizophrenia have not been established.
Safety and effectiveness of risperidone in children less than 10 years old with bipolar disorder have not been established.
Use in Elderly: Elderly patients generally have decreased renal, hepatic and cardiac function, and an increased tendency to postural hypotension. Therefore, lower starting doses, lower rates of dose adjustment and lower maximal doses are recommended in these patients.
Risperidone is substantially excreted by the kidneys. Thus, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Caution should be taken in dose selection and titration since elderly patients are more likely to have decreased real function. Monitoring of renal function in these patients is also recommended.
Patients with Parkinson's Disease or Lewy Body Dementia: Patients with Parkinson's Disease or Dementia with Lewy Bodies can experience increased sensitivity to risperidone. Manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome.
Use in Geriatric Patients with Dementia of the Alzheimer Type: Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared to a rate of about 2.6% in the placebo group. Although the cause of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drugs as opposed to some characteristics of the patients is not clear.
Concomitant Use With Furosemide: In risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%) when compared to patients treated with risperidone alone (3.1%), furosemide alone (4.1%), or placebo without furosemide (2.9%). The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed.
Nevertheless, caution should be exercised and the risks and benefits of this combination should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant medication with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be carefully avoided in elderly patients with dementia. Risperidone is not approved for the treatment of dementia-related psychosis.
Cardiovascular Adverse Events (CVAEs) in Elderly Patients with Dementia: Analysis of clinical trials in elderly patients with dementia suggests that the use of risperidone in dementia patients may be associated with an increased incidence of reports of CVAEs such as stroke and transient ischemic attacks, including fatalities. In placebo-controlled trials, there was a significantly higher incidence of CVAEs in patients treated with risperidone compared to placebo-treated patients. There is insufficient information to determine whether CVAEs in elderly patients with dementia are associated specifically with risperidone or other antipsychotic agents.
Therefore, physicians are advised to assess the risks and benefits of the use of risperidone in elderly patients with dementia taking into account risk predictors for stroke in the individual patient. Patients/caregivers should be advised to immediately report signs and symptoms of potential CVAEs such as sudden weakness or numbness in the face, arms or legs, and speech or vision problems. In placebo-controlled trials, there was a significantly higher incidence of CVAEs in patients treated with risperidone compared to placebo-treated patients. There is insufficient information to determine whether CVAEs in elderly patients with dementia are associated specifically with risperidone or other antipsychotic agents.
All treatment options should be considered without delay, including discontinuation. Furthermore, caution should be exercised in prescribing risperidone to patients with vascular comorbidities, such as hypertension and cardiovascular disease.