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LORCAINIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Lorcainide is a class Ic antiarrhythmic agent that has been used for the suppression of ventricular arrhythmias, including ventricular and supraventricular tachycardia, and premature ventricular contractions.

Specific Substances

    1) Isocainid
    2) Lorcainid
    3) Lorcainida
    4) Lorcainidum
    5) Socainid
    6) Isocainide hydrochloride
    7) R-15889
    8) RO 13-1402
    9) Socainide hydrochloride
    10) 4'-Chloro-N-(1-isopropyl-4-piperidyl)-2-phenylacetanilide
    11) hydrochloride
    12) N-(4-Chlorophenyl)-N-[1-(1-methyl-ethyl)-4-piperidinyl]
    13) benzeneacetamide
    14) Molecular Formula: C22-H27-Cl-N2-O, HCl
    15) CAS 59729-31-6 (lorcainide)
    16) CAS 58934-46-6 (lorcainide hydrochloride)
    17) R15889

Available Forms Sources

    A) FORMS
    1) Lorcainide is available in Europe as 100 mg tablets and as an intravenous solution.
    B) SOURCES
    1) Lorcainide was manufactured in Germany and the Netherlands by Janssen-Cilag, although it is no longer actively marketed.
    C) USES
    1) Lorcainide has been used for the management of ventricular and supraventricular tachycardia and premature ventricular contractions (Eirikkson.& Brogden, 1984).
    2) Lorcainide has been shown to be effective in the treatment of Wolf-Parkinson-White syndrome in children (Samanek et al, 1987).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Hypotension, ventricular dysrhythmias, CHF, hyponatremia, and CNS effects, including headache, anxiety, dizziness, and insomnia, may occur following therapeutic administration of intravenous or oral lorcainide.
    B) WITH POISONING/EXPOSURE
    1) Bradycardia, QRS widening, generalized seizures, shock, coma, and death have occurred after overdose.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Hypotension, ventricular dysrhythmias, AV blocks, QRS and QT prolongation may occur with therapeutic administration of lorcainide with exacerbation of dysrhythmias possible in patients with pre-existing cardiac abnormalities.
    B) WITH POISONING/EXPOSURE
    1) Bradycardia, hypotension, and QRS widening developed in a fatal overdose.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Insomnia is common with therapeutic use; dizziness, anxiety, tremor, ataxia, headache, and hallucinations may also occur.
    B) WITH POISONING/EXPOSURE
    1) Seizures and coma have been reported after overdose.

Laboratory Monitoring

    A) Monitor serum electrolytes.
    B) Obtain an ECG and institute continuous cardiac monitoring.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) VENTRICULAR DYSRHYTHMIAS - Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Intravenous bicarbonate may be useful in patients with QRS widening or ventricular dysrhythmias. Administer 1 to 2 mEq/kg bolus and repeat as needed. Monitor ECG and arterial blood gases; maintain pH of 7.45 to 7.55.
    1) If unresponsive to bicarbonate, lidocaine is generally first-line therapy. If dysrhythmias persist, consider phenytoin.
    E) ATROPINE: ADULT DOSE: BRADYCARDIA: BOLUS: 0.5 mg IV may repeat every 3 to 5 min. Maximum: 3 mg. PEDIATRIC DOSE: 0.02 mg/kg IV/IO (0.04 to 0.06 mg/kg ET). Repeat once, if needed. Minimum dose: 0.1 mg. Maximum single dose: Child: 0.5 mg; Adolescent: 1 mg. Maximum total dose: Child: 1 mg; Adolescent: 2 mg.
    F) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 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).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    G) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.

Range Of Toxicity

    A) Ingestion of 2500 milligrams was fatal in a healthy adolescent.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Hypotension, ventricular dysrhythmias, CHF, hyponatremia, and CNS effects, including headache, anxiety, dizziness, and insomnia, may occur following therapeutic administration of intravenous or oral lorcainide.
    B) WITH POISONING/EXPOSURE
    1) Bradycardia, QRS widening, generalized seizures, shock, coma, and death have occurred after overdose.

Heent

    3.4.3) EYES
    A) BLURRED VISION
    1) WITH THERAPEUTIC USE
    a) Blurred vision has been reported following lorcainide therapy, particularly with high intravenous doses (McDevitt, 1984; Samanek et al, 1987).
    3.4.6) THROAT
    A) METALLIC TASTE
    1) WITH THERAPEUTIC USE
    a) A metallic or bad taste has been noted (Anastasiou-Nana et al, 1985; (Echt et al, 1985).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypotension, ventricular dysrhythmias, AV blocks, QRS and QT prolongation may occur with therapeutic administration of lorcainide with exacerbation of dysrhythmias possible in patients with pre-existing cardiac abnormalities.
    B) WITH POISONING/EXPOSURE
    1) Bradycardia, hypotension, and QRS widening developed in a fatal overdose.
    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia (heart rate of 48 beats/min) with widened ventricular complexes was observed on an ECG of a 15-year-old female who ingested 2500 mg lorcainide. Despite aggressive resuscitative measures, the patient died of heart failure three hours post-ingestion (Evers & Buttner-Belz, 1995).
    B) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension may occur therapeutic administration of lorcainide (McDevitt, 1984).
    2) WITH POISONING/EXPOSURE
    a) Hypotension may occur following overdose of lorcainide (Evers & Buttner-Belz, 1995).
    C) ELECTROCARDIOGRAM ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Prolongation of the QRS and QT intervals have been reported following lorcainide therapy (Samanek et al, 1987; McDevitt, 1984; Myburgh et al, 1980; Kasper et al, 1979).
    2) WITH POISONING/EXPOSURE
    a) Prolongation of the QRS and QT intervals have been reported following an overdose ingestion of lorcainide (Evers & Buttner-Belz, 1995).
    D) VENTRICULAR ARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Ventricular dysrhythmias, including sustained ventricular tachycardia and ventricular fibrillation, have been reported with therapeutic administration of lorcainide and may be exacerbated in patients with pre-existing cardiac abnormalities (Chesnie et al, 1984) Giardina et al, 1987; (Cowley et al, 1993).
    E) HEART BLOCK
    1) WITH THERAPEUTIC USE
    a) Second and third degree heart block have been infrequently reported with oral lorcainide therapy (Cowley et al, 1993; Hanyok et al, 1987; Chesnie et al, 1984; Kasper et al, 1979).
    F) RIGHT HEART FAILURE
    1) WITH THERAPEUTIC USE
    a) Worsening congestive heart failure has occurred in patients receiving lorcainide intravenously and orally with a resolution of symptoms following administration of diuretics and the cessation of lorcainide therapy (Hanyok et al, 1987; Somani et al, 1987; Echt et al, 1985).
    b) Two patients, involved in a lorcainide efficacy trial, died after developing worsening heart failure following administration of oral lorcainide therapy (Cowley et al, 1993).
    G) DEAD - SUDDEN DEATH
    1) WITH THERAPEUTIC USE
    a) Sudden death, due to cardiogenic shock and asystole, have occurred in patients with recent myocardial infarction receiving therapeutic lorcainide (Cowley et al, 1993).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Insomnia is common with therapeutic use; dizziness, anxiety, tremor, ataxia, headache, and hallucinations may also occur.
    B) WITH POISONING/EXPOSURE
    1) Seizures and coma have been reported after overdose.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Generalized seizures occurred in a 15-year-old girl following an intentional overdose ingestion of 2500 mg lorcainide. Diazepam was given to control her seizures, however the patient died of heart failure 3 hours post-ingestion (Evers & Buttner-Belz, 1995).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) A 15-year-old girl presented to the ED unconscious and without a pulse approximately 30 minutes after an intentional overdose ingestion of 2500 mg lorcainide. Despite aggressive resuscitative measures, the patient died of heart failure 3 hours post-ingestion (Evers & Buttner-Belz, 1995).
    C) INSOMNIA
    1) WITH THERAPEUTIC USE
    a) Insomnia is a common occurrence with the oral and intravenous administration of lorcainide in adults and children (Samanek et al, 1987; Mead et al, 1985; Echt et al, 1985) and may resolve with continued use of lorcainide.
    b) Insomnia was reported in 12 of 14 patients following oral lorcainide therapy, but occurred in only 2 of 14 patients after intravenous administration of lorcainide (Vlay & Mallis, 1986).
    c) Twenty of 24 patients experienced insomnia following oral lorcainide therapy and the severity of the insomnia necessitated the discontinuation of lorcainide in 2 of the 20 patients (Anastasiou-Nana et al, 1985).
    D) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness or lightheadedness may occur with varying frequency following therapeutic administration of lorcainide (McDevitt, 1984) Anastasiou-Nana et al, 1985; (Vlay & Mallis, 1986; Samanek et al, 1987).
    E) ANXIETY
    1) WITH THERAPEUTIC USE
    a) Anxiety is an infrequent occurrence with lorcainide therapy (Anastasiou-Nana et al, 1985; (Mead et al, 1985).
    F) ATAXIA
    1) WITH THERAPEUTIC USE
    a) Ataxia and tremor were reported in 18% and 36%, respectively, of patients (n=50) involved in a lorcainide efficacy study (Echt et al, 1985).
    G) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache occurred in 7 of 24 patients (29%) who were given long-term oral lorcainide following initial intravenous administration of lorcainide to control ventricular arrhythmias (Anastasiou-Nana et al, 1985).
    H) HALLUCINATIONS
    1) WITH THERAPEUTIC USE
    a) Vivid dreams and hallucinations have been infrequently reported following oral lorcainide therapy (Cowley et al, 1993) Anastasiou-Nana et al, 1985; (Mead et al, 1985).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting may occur following therapeutic administration of lorcainide (Chesnie et al, 1984; Samanek et al, 1987; Cowley et al, 1993).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH THERAPEUTIC USE
    a) Excessive sweating, particularly at night, has been reported with oral lorcainide therapy (Anastasiou-Nana et al, 1985).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor serum electrolytes.
    B) Obtain an ECG and institute continuous cardiac monitoring.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Lorcainide serum levels are not readily available.
    2) Monitor serum electrolytes and arterial blood gases in symptomatic patients.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Obtain serial ECGs and institute continuous cardiac monitoring.

Methods

    A) CHROMATOGRAPHY
    1) High-performance liquid chromatographic methods have been described for the determination of lorcainide and its active metabolite, norlorcainide, in human plasma. The limits of sensitivity, using this method, were 5 ng/ml for both the parent drug and the metabolite (Yee & Kates, 1981; (Simon & Somani, 1982).
    2) Woestenborghs et al (1979) described a gas-liquid chromatographic method for simultaneous determination of lorcainide and its three major metabolites in human plasma, urine, feces, and tissues. The limit of sensitivity, using this method, was 5 ng/ml for lorcainide and 10 to 20 ng/ml for the three metabolites.
    3) Thin layer chromatography was used for the analysis of lorcainide in human plasma, with 0.05 mcg/ml as the lowest concentration of lorcainide found in plasma that is able to be analyzed using this method (Paw & Przyborowski, 1995).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor serum electrolytes.
    B) Obtain an ECG and institute continuous cardiac monitoring.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    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) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
    B) 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).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) VENTRICULAR ARRHYTHMIA
    1) SODIUM BICARBONATE
    a) Serum alkalinization with sodium bicarbonate may be useful in treating dysrhythmias. Administer 1 to 2 milliequivalents/kilogram as an intravenous bolus and repeat as needed to maintain arterial pH 7.45 to 7.55. Monitor ECG, arterial blood gases and electrolytes.
    b) VENTRICULAR DYSRHYTHMIAS SUMMARY
    1) 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.
    2) 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).
    3) 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).
    4) PHENYTOIN
    a) Phenytoin may be effective in patients with lorcainide-induced ventricular dysrhythmias, particularly in patients with seizures. Phenytoin loading dose can be administered concurrently with sodium bicarbonate boluses.
    b) PHENYTOIN LOADING DOSE (ADULT AND CHILD): Administer 15 to 20 milligrams/kilogram intravenously not to exceed 50 milligrams/minute (ADULT) or 1.5 milligrams/minute (CHILD) with ECG monitoring.
    c) PHENYTOIN MAINTENANCE DOSE: ADULT - administer 100 milligrams every 6 to 8 hours; CHILD - administer 4 to 7 milligrams/kilogram/day in 2 divided doses.
    5) CONTRAINDICATIONS
    a) Bretylium should be avoided due to the worsening of hypotension as a result of its alpha-blocking activity. Avoid type IA antiarrhythmic agents (i.e., quinidine, procainamide, disopyramide) because they may worsen dysrhythmias.
    B) BRADYCARDIA
    1) ATROPINE/DOSE
    a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
    b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.
    1) There is no minimum dose (de Caen et al, 2015).
    2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
    2) ISOPROTERENOL INDICATIONS
    a) Used for temporary control of hemodynamically significant bradycardia in a patient with a pulse; generally other modalities (atropine, dopamine, epinephrine, dobutamine, pacing) should be used first because of the tendency to develop ischemia and dysrhythmias with isoproterenol (Neumar et al, 2010).
    b) ADULT DOSE: Infuse 2 micrograms per minute, gradually titrating to 10 micrograms per minute as needed to desired response (Neumar et al, 2010).
    c) CAUTION: Decrease infusion rate or discontinue infusion if ventricular dysrhythmias develop(Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    d) PEDIATRIC DOSE: Not well studied. Initial infusion of 0.1 mcg/kg/min titrated as needed, usual range is 0.1 mcg/kg/min to 1 mcg/kg/min (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    3) CARDIAC PACING may be useful in patients with persistent bradycardia not responsive to other measures.
    4) Consider cardiopulmonary bypass in patients not responsive to other measures. This may provide hemodynamic support allowing continued metabolism of lorcanide and eventual resolution of toxicity.
    C) 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, 2009; 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).
    D) HYPOTENSIVE EPISODE
    1) 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.
    2) 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).
    3) 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).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Lorcainide is highly protein-bound and has a large volume of distribution, therefore it is unlikely that hemodialysis will be effective.

Range Of Toxicity

Summary

    A) Ingestion of 2500 milligrams was fatal in a healthy adolescent.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) ORAL - Usual starting dose is 100 milligrams twice daily with a maintenance dose of 100 to 400 milligrams daily (Eiriksson & Brogden, 1984).
    2) INTRAVENOUS - The usual initial dose is approximately 2 milligrams/kilogram usually given over 10 to 20 minutes at a rate of 10 milligrams/minute. A maintenance infusion, for effective therapeutic concentrations, may be given at a rate of 0.18 to 0.27 milligrams/kilogram/hour (Eiriksson & Brogden, 1994).

Minimum Lethal Exposure

    A) PEDIATRIC
    1) CASE REPORT - A 15-year-old girl intentionally ingested 2500 milligrams of lorcainide and, approximately 30 minutes later, presented to the ED comatose and without a pulse. The ECG showed bradycardia with widened ventricular complexes. Despite aggressive resuscitative measures, the patient died of heart failure 3 hours post-ingestion (Evers & Buttner-Belz, 1995).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) The therapeutic serum concentration level of lorcainide is 150 to 400 nanograms/milliliter (Evers & Buttner-Belz, 1995).
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) The serum lorcainide concentration in a 15-year-old girl, approximately 30 to 60 minutes after ingestion of 2500 milligrams, was 1820 nanograms/ milliliter (therapeutic range 150 to 400 nanograms/milliliter). The serum concentration of norlorcainide, the active metabolite, was 450 nanograms/ milliliter (Evers & Buttner-Belz, 1995).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 483 mg/kg (RTECS, 1999)
    B) LD50- (ORAL)RAT:
    1) 395 mcg/kg (RTECS, 1999)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Lorcainide, a synthetic acetanilide derivative with class Ic antiarrhythmic activity, has electrophysiologic actions that result in decreases in the phase 0 of depolarization, amplitude of action potential, and conduction velocity, and in prolongation of the action potential duration (Anastasiou-Nana et al, 1985).

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