Medications: Risperdal^® – risperidone

RISPERDAL® is an atypical antipsychotic indicated for:

• Treatment of schizophrenia (1.1)
• As monotherapy or adjunctive therapy with lithium or valproate, for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder (1.2)
• Treatment of irritability associated with autistic disorder (1.3)

DOSAGE AND ADMINISTRATION

• Severe Renal or Hepatic Impairment in Adults: Use a lower starting dose of 0.5 mg twice daily. May increase to dosages above 1.5 mg twice daily at intervals of at least one week. (2.4)
• Oral Solution: Can be administered directly from calibrated pipette or mixed with beverage (water, coffee, orange juice, or low-fat milk). (2.6)
• M-TAB Orally Disintegrating Tablets: Open the blister only when ready to administer, and immediately place tablet on the tongue. Can be swallowed with or without liquid. (2.7)

The most common adverse reactions in clinical trials (>5% and twice 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. (6)

Known hypersensitivity to risperidone, paliperidone, or to any excipients in RISPERDAL®. (4)

WARNINGS AND PRECAUTIONS:

• Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis: RISPERDAL® is not approved for use in patients with dementia-related psychosis. (5.2)
• Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of RISPERDAL® and close monitoring. (5.3)
• Tardive dyskinesia: Consider discontinuing RISPERDAL® if clinically indicated. (5.4)
• Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.5)
• Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. (5.5)
• Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.5)
• Weight Gain: Significant weight gain has been reported. Monitor weight gain. (5.5)
• Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration. (5.6)
• Orthostatic hypotension: For patients at risk, consider a lower starting dose and slower titration. (5.7) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts in patients with a history of clinically significant low white blood cell count (WBC). Consider discontinuing RISPERDAL® if a clinically significant decline in WBC occurs in the absence of other causative factors. (5.9)
• Potential for cognitive and motor impairment: Use caution when operating machinery. (5.10)
• Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.11)

• Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. Increase the RISPERDAL^® dose up to double the patient’s usual dose. Titrate slowly. (7.1)
• Fluoxetine, paroxetine, and other CYP 2D6 enzyme inhibitors increase plasma concentrations of risperidone. Reduce the initial dose. Do not exceed a final dose of 8 mg per day of RISPERDAL^®. (7.1)

Premarketing experience included eight reports of acute RISPERDAL overdosage with estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the drug’s known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. One case, involving an estimated overdose of 240 mg, was associated with hyponatremia, hypokalemia, prolonged QT, and widened QRS. Another case, involving an estimated overdose of 36 mg, was associated with a seizure.

Postmarketing experience includes reports of acute RISPERDAL overdosage, with estimated doses of up to 360 mg. In general, the most frequently reported signs and symptoms are those resulting from an exaggeration of the drug’s known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Other adverse reactions reported since market introduction related to RISPERDAL overdose include prolonged QT interval and convulsions. Torsade de pointes has been reported in association with combined overdose of RISPERDAL and paroxetine. 10.2

Management of Overdosage: For the most up to date information on the management of RISPERDAL overdosage, contact a certified poison control center (1-800-222-1222 or www.poison.org). Provide supportive care including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures. There is no specific antidote to RISPERDAL.