- USES: An atypical antipsychotic used to treat schizophrenia. PHARMACOLOGY: A benzisoxazole derivative with high antagonist affinity for dopamine (D2) and serotonin (5-HT2) receptors. TOXICOLOGY: Dopamine receptor blockade results in extrapyramidal symptoms, and alpha1-adrenergic effects are responsible for orthostatic hypotension. Its affinity, albeit low affinity, for histamine receptors contributes to anticholinergic effects. EPIDEMIOLOGY: Unintentional and deliberate poisonings of atypical antipsychotics are common and occasionally severe. MILD TO MODERATE TOXICITY: Tachycardia and hypotension are common. Depressed mental status, somnolence and extrapyramidal symptoms are also fairly common. In most cases, symptoms manifest mainly as mild central nervous system effects and reversible cardiovascular and neuromuscular effects. SEVERE TOXICITY: QTc prolongation, extrapyramidal symptoms likely. Respiratory depression, seizure, or coma could potentially occur, as well as neuroleptic malignant syndrome. ADVERSE EFFECTS: COMMON: Nausea, diarrhea, constipation, dizziness, somnolence, tachycardia, orthostatic hypotension, and extrapyramidal disorder.
Range of Toxicity:
- TOXICITY: SUMMARY: CHILD: In drug naive children, an ingestion of 1 mg in a child less than 12 years of age should be considered potentially toxic, and an ingestion of more than 5 mg should be considered potentially toxic in a child 12 years or older. In children who are using risperiDONE on a regular basis, a does of more than 5 times their current single dose (not daily dose) should be considered potentially toxic. ADULT: Overdose of 270 mg in an adult resulted in dysrhythmias (supraventricular tachycardia, atrial flutter, prolonged QTc, bradycardia) and extrapyramidal symptoms. An adult developed tachycardia and QTc prolongation after ingesting an estimated dose of greater than 60 mg of risperiDONE. Another adult developed rhabdomyolysis after an intentional mixed ingestion that included 96 mg of risperiDONE; recovery was uneventful following supportive care. PEDIATRIC: A 15-year-old girl developed transient lethargy, hypotension, and tachycardia after ingesting 110 mg of risperiDONE. THERAPEUTIC DOSE: ADULT: 4 to 16 mg/day, with therapeutic effects usually in the range of 4 to 6 mg/day.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Management will primarily be symptomatic and supportive. Treat seizures with benzodiazepines. Manage mild hypotension with IV fluids. MANAGEMENT OF SEVERE TOXICITY: Treat seizures with benzodiazepines. Treat hypotension with IV fluids and pressors (norepinephrine preferred) if needed. Treat ventricular dysrhythmias with sodium bicarbonate, use lidocaine or amiodarone if bicarbonate unsuccessful. Manage severe extrapyramidal symptoms with anticholinergics and/or benzodiazepines. Although rare, treat neuroleptic malignant syndrome with benzodiazepines, bromocriptine, consider dantrolene, as well as cooling and supportive measures.
- Decontamination: PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended due to the potential for somnolence, seizures and dystonic reaction. HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
- Airway management: Insure adequate ventilation and perform endotracheal intubation early in patients with serious cardiac toxicity, coma or significant CNS depression.
- Antidote: None
- Seizure: Administer IV benzodiazepines; add propofol, or barbiturates if seizures recur or persist.
- Hypotensive episode: Treat hypotension with intravenous fluids, if hypotension persists administer vasopressors. Norepinephrine is preferred; the manufacturer recommends avoidance of epinephrine and dopamine since beta stimulation may worsen hypotension in the setting of risperiDONE-induced alpha blockade.
- Conduction disorder of the heart: Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Sodium bicarbonate is generally first line therapy for QRS widening and ventricular dysrhythmias, administer 1 to 2 mEq/kg, repeat as needed to maintain blood pH between 7.45 and 7.55. In patients unresponsive to bicarbonate, consider lidocaine or amiodarone.
- Neuroleptic malignant syndrome: Oral bromocriptine, benzodiazepines or oral or IV dantrolene in conjunction with cooling and other supportive measures.
- Monitoring of patient: Monitor vital signs and mental status. Obtain an ECG and institute continuous cardiac monitoring. Monitor serum electrolytes including sodium, potassium, and magnesium, as well as glucose; obtain CBC.
- Enhanced elimination procedure: Hemodialysis and hemoperfusion are UNLIKELY to be of value because of the high degree of protein binding.
- Patient disposition: HOME CRITERIA: Children less than 12 years of age who are naive to risperiDONE can be observed at home following an unintentional ingestion of 1 mg or less and are only experiencing mild sedation. All patients, 12 years of age or older, who are naive to risperiDONE, can be observed at home following an unintentional ingestion of 5 mg or less and are experiencing only mild sedation. All patients who are taking risperiDONE on a chronic basis can be observed at home if they have unintentionally ingested no more than 5 times their current single dose (not daily dose) of risperiDONE and are only experiencing mild sedation. Patients who have not developed signs or symptoms more than 6 hours after ingestion are unlikely to develop toxicity. OBSERVATION CRITERIA: Any patient with a deliberate ingestion or more than minor symptoms should be referred to a healthcare facility. Children less than 12 years of age who are naive to risperiDONE should be referred to a healthcare facility following an unintentional ingestion of more than 1 mg. All patients, 12 years of age or older, who are naive to risperiDONE should be referred to a healthcare facility following an unintentional ingestion of more than 5 mg. All patients who are taking risperiDONE on a chronic basis should be referred to a healthcare facility following an acute ingestion of more than 5 times their current single dose (not daily dose) of risperiDONE. ADMISSION CRITERIA: Patients with deliberate ingestions demonstrating cardiotoxicity, or persistent neurotoxicity should be admitted. CONSULT CRITERIA: Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.