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ATYPICAL NEUROLEPTICS

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Atypical neuroleptics differ from other neuroleptics in their binding to dopamine receptors and their effects on dopamine-mediated behaviors.
    B) Refer to CLOZAPINE, RISPERIDONE, ZIPRASIDONE, OLANZAPINE, QUETIAPINE, ARIPIPRAZOLE, OR LURASIDONE documents for more information.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Clothiapine
    2) Remoxipride
    3) Sertindole

Available Forms Sources

    A) FORMS
    1) REMOXIPRIDE: Roxiam(R) (remoxipride) is being withdrawn from worldwide markets by Astra Pharmaceutical Products due to reports of aplastic anemia associated with remoxipride use. The drug will, however, remain available for compassionate use.
    2) SERTINDOLE is in clinical trials in the United States with Abbott Laboratories as Serlect(R) (Anon, 1996; 58). The manufacturer of sertindole (Serdolect(R), Lundbeck Ltd.) is voluntarily suspending its availability as of December 2, 1998. This suspension is due to reports of cardiac arrhythmias and sudden cardiac death associated with its use. H. Promonta Denmark and associated European manufacturers temporarily suspended distribution of their sertindole product Serdolect(R) in December 1998(Anon, 1998). Subsequent analysis of this data indicated that sertindole was no more likely to cause serious adverse drug reactions in schizophrenic patients than any of the other currently available antipsychotic medications. Sertindole was reintroduced to the market in 2002 (Kasper, 2002).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) REMOXIPRIDE -
    1) Overdosage of up to 2500 milligrams produced only extrapyramidal symptoms in one group of patients. The most common adverse effects of therapeutic use include drowsiness, tremors, and akathisia.
    2) Therapeutic use of remoxipride has NOT generally been associated with sedation, clinically evident hypotension, cardiovascular, or extrapyramidal adverse effects. In clinical trials, rare cases of myocardial infarction, seizures, aggressiveness, hypertension, liver function abnormality, and postural hypotension were reported with therapeutic doses.
    0.2.3) VITAL SIGNS
    A) REMOXIPRIDE - Orthostatic hypotension may occur with overdose; one case of hypertension during therapeutic use has been reported.
    0.2.5) CARDIOVASCULAR
    A) REMOXIPRIDE - Orthostatic hypotension may occur with overdose. One case of myocardial infarction during therapeutic use has been reported.
    0.2.7) NEUROLOGIC
    A) REMOXIPRIDE - Drowsiness, sedation, and seizures may occur with overdose.
    0.2.14) DERMATOLOGIC
    A) REMOXIPRIDE - One case of a generalized skin reaction has been reported.

Laboratory Monitoring

    A) Monitor acid-base status, fluid and electrolyte balance, hepatic enzyme levels (serum ALP, SGOT, and SGPT), renal function and urine output.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Transport any suspected overdose patient to a health care facility as soon as possible. Admit any patient with clinical signs of phenothiazine overdose.
    1) Take careful patient history to determine previous exposure and present exposure to neuroleptic agents. DO NOT induce emesis. Administer activated charcoal.
    2) Positioning and intravenous fluids are sufficient treatment for hypotension in most patients. If pressors are needed dopamine, or more selective alpha agonists (norepinephrine, phenylephrine or metaraminol) should be considered. Be prepared to treat seizures in patients with CNS excitation.
    3) Treat ventricular tachydysrhythmias with sodium bicarbonate (1 to 2 mEq/kg starting dose, repeat as needed to maintain arterial pH 7.45-7.55), followed by lidocaine or amiodarone; then pacing if needed.
    4) Treat neuroleptic malignant syndrome with dantrolene or bromocriptine along with conservative treatment.
    5) RHABDOMYOLYSIS: Administer sufficient 0.9% saline (10 to 15 mL/kg/hour) to maintain urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hr). Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output, but should only be considered if urine output is inadequate after volume status is restored. Urinary alkalinization is NOT routinely recommended.

Range Of Toxicity

    A) REMOXIPRIDE - Overdose of up to 2500 milligrams generally results in extrapyramidal symptoms only. Fatal overdose of remoxipride alone has occurred (amount ingested was unspecified).

Summary Of Exposure

    A) REMOXIPRIDE -
    1) Overdosage of up to 2500 milligrams produced only extrapyramidal symptoms in one group of patients. The most common adverse effects of therapeutic use include drowsiness, tremors, and akathisia.
    2) Therapeutic use of remoxipride has NOT generally been associated with sedation, clinically evident hypotension, cardiovascular, or extrapyramidal adverse effects. In clinical trials, rare cases of myocardial infarction, seizures, aggressiveness, hypertension, liver function abnormality, and postural hypotension were reported with therapeutic doses.

Vital Signs

    3.3.1) SUMMARY
    A) REMOXIPRIDE - Orthostatic hypotension may occur with overdose; one case of hypertension during therapeutic use has been reported.
    3.3.4) BLOOD PRESSURE
    A) ORTHOSTATIC HYPOTENSION has been reported in patients taking remoxipride therapeutically (Kane, 1993; Patris et al, 1990).
    B) HYPERTENSION - One case has been reported in a patient taking remoxipride therapeutically (Patris et al, 1990) and may also occur with overdose.

Cardiovascular

    3.5.1) SUMMARY
    A) REMOXIPRIDE - Orthostatic hypotension may occur with overdose. One case of myocardial infarction during therapeutic use has been reported.
    3.5.2) CLINICAL EFFECTS
    A) MYOCARDIAL INFARCTION
    1) REMOXIPRIDE - Myocardial infarction was reported in 1 of 179 patients in therapeutic clinical trials of remoxipride (Lapierre et al, 1990).
    2) SERTINDOLE - Treatment with sertindole was associated with a significant dose-related increase in QT interval compared to placebo in a controlled trial. The increase was not directly associated with any adverse events and did not exceed 500 milliseconds (Brown & Levin, 1998).

Neurologic

    3.7.1) SUMMARY
    A) REMOXIPRIDE - Drowsiness, sedation, and seizures may occur with overdose.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) Drowsiness or sedation are adverse effects of therapeutic remoxipride doses (Kane, 1993).
    B) SEIZURE
    1) Remoxipride therapy was associated with seizures in 2 of 179 patients followed (Lapierre et al, 1990); overdose may predispose patients to seizures.
    C) NEUROLEPTIC MALIGNANT SYNDROME
    1) CASE SERIES - Neuroleptic malignant syndrome was reported in 4 patients treated with clothiapine. Each patient manifested a prodromal catatonic state before onset of NMS (White & Robins, 1991).
    2) EFFECTS - Include rigidity, hyperthermia, mental status depression, autonomic instability, elevated creatinine phosphokinase, tachycardia, tachypnea, hypertension, sweating, and leukocytosis.

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) Sertindole therapy has resulted in increased liver enzymes (Brown & Levin, 1998).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL EJACULATION
    1) Decreased ejaculatory volume was reported significantly more with sertindole treatment compared to haloperidol or placebo. In one study, the incidence was 17% in patients receiving sertindole 20 mg/day compared to 2% for placebo (Brown & Levin, 1998).

Dermatologic

    3.14.1) SUMMARY
    A) REMOXIPRIDE - One case of a generalized skin reaction has been reported.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) REMOXIPRIDE - One of 179 patients entered in therapeutic trials of remoxipride developed a generalized skin reaction (Lapierre et al, 1990).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor acid-base status, fluid and electrolyte balance, hepatic enzyme levels (serum ALP, SGOT, and SGPT), renal function and urine output.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor acid-base status, fluid and electrolyte balance, hepatic enzyme levels (serum ALP, SGOT, and SGPT) and renal function.
    B) ACID/BASE
    1) Monitor acid-base status.
    4.1.3) URINE
    A) OTHER
    1) Monitor urine output.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Institute continuous cardiac monitoring and obtain ECG.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor acid-base status, fluid and electrolyte balance, hepatic enzyme levels (serum ALP, SGOT, and SGPT), renal function and urine output.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Emesis is not recommended because of the possibility of a dystonic reaction or CNS depression and subsequent aspiration.
    B) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) HYPOTENSIVE EPISODE
    1) CHOICE OF VASOPRESSORS - Fluid challenge is sufficient for correction of hypotension in most patients. If hypotension does not respond to dopamine, an agent with more selective alpha adrenergic activity is a logical second choice (norepinephrine, metaraminol).
    2) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    3) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    4) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    C) CONDUCTION DISORDER OF THE HEART
    1) VENTRICULAR TACHYCARDIA - The major arrhythmia likely to occur.
    a) Ventricular tachydysrhythmias due to phenothiazine toxicity should be managed like quinidine-induced ventricular tachycardia: administration of sodium bicarbonate, lidocaine, followed by pacing if needed.
    2) SERUM ALKALINIZATION
    a) Sodium bicarbonate has been used to reverse ventricular dysrhythmias and QRS widening from a variety of toxins with sodium channel blocking effects. An initial sodium bicarbonate dose of 1 to 2 mEq/kilogram is reasonable, repeat as needed to achieve an arterial pH of 7.45 to 7.55. Institute continuous cardiac monitoring, obtain serial ECGs and electrolytes, and monitor arterial blood gases.
    3) VENTRICULAR DYSRHYTHMIAS SUMMARY
    a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    4) LIDOCAINE -
    a) LIDOCAINE/INDICATIONS
    1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).
    b) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    c) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    d) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    5) AMIODARONE -
    a) AMIODARONE/INDICATIONS
    1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
    b) AMIODARONE/ADULT DOSE
    1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).
    c) AMIODARONE/PEDIATRIC DOSE
    1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
    d) ADVERSE EFFECTS
    1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).
    6) PHENYTOIN DOSE -
    a) PHENYTOIN LOADING DOSE (ADULT and CHILD) - Administer 15 milligrams/kilogram up to 1 gram intravenously not to exceed a rate of 0.5 milligram/kilogram/minute.
    b) PHENYTOIN MAINTENANCE DOSE - ADULT - administer 2 milligrams/kilogram intravenously every 12 hours as needed; CHILD - administer 2 milligrams/kilogram intravenously every 8 hours as needed.
    c) MONITOR SERUM PHENYTOIN LEVELS - just prior to initiating and during maintenance therapy to assure therapeutic levels of 10 to 20 micrograms/milliliter.
    1) A loading dose as above should provide therapeutic levels for over 12 hours. This method of dosing avoids marked sinus slowing, profound hypotension and cardiac arrest.
    D) NEUROLEPTIC MALIGNANT SYNDROME
    1) May be successfully managed with intravenous or oral dantrolene sodium, diphenhydramine, oral bromocriptine, or benzodiazepines in conjunction with cooling and other supportive care (May et al, 1983; Mueller et al, 1983; Leikin et al, 1987; Schneider, 1991; (Barkin, 1992).
    a) DANTROLENE LOADING DOSE - 2.5 milligrams/kilogram, to a maximum of 10 milligrams/kilogram intravenously (Barkin, 1992).
    b) DANTROLENE MAINTENANCE DOSE - 2.5 milligrams/kilogram intravenously every 6 hours (Barkin, 1992); 1 milligram/kilogram orally every 12 hours, up to 50 milligrams/dose has also been successful (May et al, 1983).
    c) BROMOCRIPTINE DOSE - 5 milligrams three times a day orally (Mueller et al, 1983).
    d) Benzodiazepines are not recommended as primary agents, but may be needed to control agitated or psychotic patient (Gratz et al, 1992; Caroff & Mann, 1993). They may be used in milder cases (Kontaxakis et al, 1988).
    1) DIAZEPAM DOSE - 3 to 5 milligrams intravenous bolus to slow push initially, followed by 1 to 2.5 milligrams intravenously in 10 minutes.
    e) NON-PHARMACOLOGIC METHODS - Rapid cooling, hydration, and serial assessment of respiratory, cardiovascular, renal and neurologic function, and fluid status are used in conjunction with drug therapy and discontinuation of the neuroleptic agent (Knight & Roberts, 1986).
    2) In a review of 67 case reports of neuroleptic malignant syndrome, the onset of clinical response was shorter after treatment with DANTROLENE (mean 1.15 days) or BROMOCRIPTINE (1.03 days) than with supportive measures alone (6.8 days).
    a) The time to complete resolution was also shorter with these therapeutic interventions (Rosenberg & Green, 1989).
    3) The intravenous administration of dopamine has also been reported to be effective in two case reports (Ungvari, 1987; Ryken & Merrell, 1989).
    4) RETROSPECTIVE STUDY - A study comparing 438 untreated patients with neuroleptic malignant syndrome and 196 treated cases found that administration of dantrolene, bromocriptine, or amantadine significantly reduced the death rate in these cases (Sakkas et al, 1991).
    a) Death rate of untreated cases was 21 percent; administration of dantrolene alone (no dosage reported) decreased death rate to 8.6 percent (n=58); with bromocriptine alone death rate was 7.8 percent (n=51); and with amantadine alone death rate was 5.9 percent (n=17).
    b) In combination with other drugs, each of these drugs significantly decreased the NMS-related death rate, although the decrease was slightly less than for single administrations.
    E) RHABDOMYOLYSIS
    1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    6) MANNITOL/INDICATIONS
    a) Osmotic diuretic used in the management of rhabdomyolysis and myoglobinuria (Zimmerman & Shen, 2013).
    7) RHABDOMYOLYSIS/MYOGLOBINURIA
    a) ADULT: TEST DOSE: (for patients with marked oliguria or those with inadequate renal function) 0.2 g/kg IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase within 2 to 3 hours. The patient should be reevaluated if there is inadequate response following the second test dose (Prod Info MANNITOL intravenous injection, 2009). TREATMENT DOSE: 50 to 100 g IV as a 15% to 25% solution may be used. The rate should be adjusted to maintain urinary output at 30 to 50 mL/hour (Prod Info mannitol IV injection, urologic irrigation, 2006) OR 300 to 400 mg/kg or up to 100 g IV administered as a single dose (Prod Info MANNITOL intravenous injection, 2009).
    b) PEDIATRIC: Dosing has not been established in patients less than 12 years of age(Prod Info Mannitol intravenous injection, 2009). TEST DOSE (for patients with marked oliguria or those with inadequate renal function): 0.2 g/kg or 6 g/m(2) body surface area IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase; TREATMENT DOSE: 0.25 to 2 g/kg or 60 g/m(2) body surface area IV as a 15% to 20% solution over 2 to 6 hours; do not repeat dose for persistent oliguria (Prod Info MANNITOL intravenous injection, 2009).
    8) ADVERSE EFFECTS
    a) Fluid and electrolyte imbalance, in particular sodium and potassium; expansion of the extracellular fluid volume leading to pulmonary edema or CHF exacerbations(Prod Info MANNITOL intravenous injection, 2009).
    9) PRECAUTION
    a) Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia; do not add to whole blood for transfusions(Prod Info Mannitol intravenous injection, 2009); enhanced neuromuscular blockade observed with tubocurarine(Miller et al, 1976).
    10) MONITORING PARAMETERS
    a) Renal function, urine output, fluid balance, serum potassium, serum sodium, and serum osmolality (Prod Info Mannitol intravenous injection, 2009).
    F) SUPPORT
    1) Monitor fluid and electrolyte balance closely.
    2) Keep warm to avoid hypothermia.

Summary

    A) REMOXIPRIDE - Overdose of up to 2500 milligrams generally results in extrapyramidal symptoms only. Fatal overdose of remoxipride alone has occurred (amount ingested was unspecified).

Therapeutic Dose

    7.2.1) ADULT
    A) REMOXIPRIDE
    1) The recommended oral dose is 100 to 600 mg daily (Patris et al, 1990).
    2) Note: Roxiam(R) (remoxipride) was withdrawn from worldwide markets by Astra Pharmaceutical Products due to reports of aplastic anemia associated with remoxipride use. The drug will, however, remain available for compassionate use.

Minimum Lethal Exposure

    A) SPECIFIC SUBSTANCE
    1) REMOXIPRIDE - Fatal overdose of remoxipride alone has occurred (amount ingested was unspecified) (Morrison et al, 1990).

Maximum Tolerated Exposure

    A) SPECIFIC SUBSTANCE
    1) REMOXIPRIDE -
    a) Overdosage of up to 2500 milligrams generally results in extrapyramidal symptoms only (Morrison et al, 1990).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) SPECIFIC SUBSTANCE
    a) REMOXIPRIDE
    1) One case of a fatal remoxipride overdose has been reported. The patient's plasma remoxipride concentration was 70 to 180 times the trough level after therapeutic dosage (Morrison et al, 1990).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) REMOXIPRIDE
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 324 mg/kg (RTECS, 2001)

Pharmacologic Mechanism

    A) LURASIDONE: Lurasidone hydrochloride is an atypical antipsychotic agent that acts as an antagonist at dopamine type-2 (D2) and 5-hydroxytryptamine (5-HT)2A receptors. Lurasidone hydrochloride also has moderate antagonistic activity at alfa-2C and alfa-2A adrenergic receptors and is a partial agonist at 5-HT1A receptors. It exhibits minimal or no affinity for histamine type-1 (H1) or muscarinic type-1 (M1) receptors (Prod Info LATUDA(R) oral tablets, 2010).
    B) REMOXIPRIDE is a substituted benzamide (similar to sulpiride). It is a weak D2 antagonist and potent sigma antagonist. Other classic neuroleptic agents can block cholinergic, adrenergic, and histaminergic receptors in the brain, producing adverse effects such as postural hypotension, dry mouth, fatigue, and sedation (den Boer et al, 1987). Remoxipride reportedly does not interact with alpha-adrenergic, beta-adrenergic, serotonergic, histaminergic, or muscarinic receptors (Hall et al, 1986) Andersson et al, 1988; (Danielsson et al, 1985), which should result in a lower incidence or absence (den Boer et al, 1987) of these effects.

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    3) Anon: PMSI Research Solutions Update, Product Research and Approval Report, Vol XVI, No 1; p 2. Walsh America/PMSI, Phoenix, AZ, 1996.
    4) Anon: Serdolect - Information. Arzneimittelkommission der Deutschen Apotheker- Meldung (Dec 2), 1998.
    5) Anon: The Pink Sheet. FDC Reports (June 3), 58:T&G 20, 1996b.
    6) Barkin RM: Pediatric Emergency Medicine, Mosby YearBook, St Louis, MO, 1992, pp 500.
    7) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    8) Brown CV, Rhee P, Chan L, et al: Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference?. J Trauma 2004; 56(6):1191-1196.
    9) Brown LA & Levin GM: Sertindole, a new atypical antipsychotic for the treatment of schizophrenia. Pharmacother 1998; 18:69-83.
    10) Camp NE: Drug- and toxin-induced Rhabdomyolysis. J Emerg Nurs 2009; 35(5):481-482.
    11) Caroff SN & Mann SC: Neuroleptic malignant syndrome. Med Clin North Am 1993; 77:185-203.
    12) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    13) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    14) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    15) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    16) Criddle LM: Rhabdomyolysis. Pathophysiology, recognition, and management. Crit Care Nurse 2003; 23(6):14-22, 24-26, 28.
    17) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    18) Danielsson E, Peterson LL, & Grundin R: Anticholinergic potency of psychoactive drugs in human and rat cerebral cortex and striatum. Life Sci 1985; 36:1451-1457.
    19) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    20) Erdman AR & Dart RC: Rhabdomyolysis. In: Dart RC, Caravati EM, McGuigan MA, et al, eds. Medical Toxicology, 3rd ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2004, pp 123-127.
    21) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    22) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    23) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    24) Gratz SS, Levinson DF, & Simpson GM: The treatment and management of neuroleptic malignant syndrome. Prog Neuro-Psychopharmacol Biol Psychiat 1992; 16:425-443.
    25) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    26) Hall H, Sallemark M, & Jerning E: Effects of remoxipride and some related new substituted salicylamides on rat brain receptors. Acta Pharmacol Toxicol 1986; 58:61-70.
    27) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    28) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    29) Homsi E, Barreiro MF, Orlando JM, et al: Prophylaxis of acute renal failure in patients with rhabdomyolysis. Ren Fail 1997; 19(2):283-288.
    30) Huerta-Alardin AL, Varon J, & Marik PE: Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care 2005; 9(2):158-169.
    31) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    32) Kane JM: Newer antipsychotic drugs: a review of their pharmacology and therapeutic potential. Drugs 1993; 46:585-593.
    33) Kasper S: Favourable benefit/risk ratio enables re-introduction of sertindole (editorial). Int J Psychiatry Clin Pract 2002; 6(Suppl 1):S1-S2.
    34) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    35) Knight ME & Roberts RJ: Phenothiazine and butyrophenone intoxication in children. Pediatr Clin North Am 1986; 33:299-309.
    36) Kontaxakis VP, Christodoulou GH, & Markidis MP: Treatment of a mild form of neuroleptic malignant syndrome with oral diazepam. Acta Psychiatr Scand 1988; 78:396-398.
    37) Lapierre YD, Nair NPV, & Chouinard G: A controlled dose-ranging study of remoxipride and haloperidol in schizophrenia--a Canadian multicentre trial. Acta Psychiatrica Scand 1990; 82:72-77.
    38) Link MS, Berkow LC, Kudenchuk PJ, et al: Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S444-S464.
    39) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    40) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    41) Miller RD, Sohn YJ, & Matteo RS: Enhancement of d-tubocurarine neuromuscular blockade by diuretics in man. Anesthesiology 1976; 45:442-445.
    42) Morrison D, Englund A, & Lawrie V: Safety evaluation in both short- and long-term treatment of schizophrenia with remoxipride. Acta Psychiatrica Scand 1990; 182:164-169.
    43) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S729-S767.
    44) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    45) Patris M, Agussol P, & Alby JM: A double-blind multicentre comparison of remoxipride, at two dose levels, and haloperidol. Acta Psychiatrica Scand 1990; 82:78-82.
    46) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    47) Polderman KH: Acute renal failure and rhabdomyolysis. Int J Artif Organs 2004; 27(12):1030-1033.
    48) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    49) Product Information: Cordarone(R) oral tablets, amiodarone HCl oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadelphia, PA, 2015.
    50) Product Information: LATUDA(R) oral tablets, lurasidone HCl oral tablets. Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 2010.
    51) Product Information: Lidocaine HCl intravenous injection solution, lidocaine HCl intravenous injection solution. Hospira (per manufacturer), Lake Forest, IL, 2006.
    52) Product Information: MANNITOL intravenous injection, mannitol intravenous injection. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2009.
    53) Product Information: Mannitol intravenous injection, mannitol intravenous injection. American Regent, Inc. (per DailyMed), Shirley, NY, 2009.
    54) Product Information: benztropine mesylate IV, IM injection, benztropine mesylate IV, IM injection. West-ward Pharmaceutical Corp, Eatontown, NJ, 2009.
    55) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    56) Product Information: diphenhydramine hcl injection, diphenhydramine hcl injection. Bioniche Pharma USA,LLC, Lake Forest, IL, 2006.
    57) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    58) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    59) Product Information: mannitol IV injection, urologic irrigation, mannitol IV injection, urologic irrigation. Abraxis Pharmaceutical Products, Schaumburg, IL, 2006.
    60) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    61) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    62) Rosenberg MR & Green M: Neuroleptic malignant syndrome: Review of response to therapy. Arch Intern Med 1989; 149:1927-1931.
    63) Ryken TC & Merrell AN: Haloperidol-induced neuroleptic malignant syndrome in a 67-year-old woman with parkinsonism. West J Med 1989; 151:326-328.
    64) Sakkas P, Davis JM, & Janicak PG: Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull 1991; 27:381-384.
    65) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    66) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    67) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2010; 14(2):162-168.
    68) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    69) Ungvari GA: Treatment of neuroleptic malignant syndrome with dopamine hydrochloride: a case report. Pharmacopsychiatry 1987; 20:120-121.
    70) Vanden Hoek TL, Morrison LJ, Shuster M, et al: Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S829-S861.
    71) Vanholder R, Sever MS, Erek E, et al: Rhabdomyolysis. J Am Soc Nephrol 2000; 11(8):1553-1561.
    72) Walter LA & Catenacci MH: Rhabdomyolysis. Hosp Physician 2008; 44(1):25-31.
    73) Zimmerman JL & Shen MC: Rhabdomyolysis. Chest 2013; 144(3):1058-1065.
    74) de Caen AR, Berg MD, Chameides L, et al: Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S526-S542.
    75) den Boer JA, Verhoeven WMA, & Westenberg HGM: Remoxipride, a novel atypical neuroleptic, in the treatment of schizophrenia. Psychopharmacol Bull 1987; 23:206-210.