a) CASE REPORT: Following an inadvertent overdose of 3300 mg of oxcarbazepine over a one day period (normal dose, 2400 mg/day), a 38-year-old woman developed bradycardia (heart rate, 27 bpm) and hypotension. The patient recovered following administration of IV fluids and atropine (1 mg IV) (Jolliff et al, 2001).

a) CASE REPORT: A 38-year-old woman developed hypotension (systolic pressure of 60 mmHg) and bradycardia following an inadvertent overdose of oxcarbazepine 3300 mg over a one day period (normal dose, 2400 mg/day). She recovered following administration of IV fluids and atropine (1 mg IV) (Jolliff et al, 2001).

a) Upper respiratory tract infection has been reported in 10% of patients (n=86) in clinical trials (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Cough was reported in 5% and 0% of patients treated with oxcarbazepine doses of 2400 mg/day (n=86) and 300 mg/day (n=86), respectively, in a controlled clinical trial of adult patients converted to either high- or low-dose oxcarbazepine from other antiepileptic drugs (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Oxcarbazepine appears to have a narrow therapeutic index in regards to CNS effects (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011). Headache (adults, 13% to 32%; pediatrics, 31%), drowsiness, dizziness (adults, 8% to 49%; pediatrics, 28%), ataxia (adults, 1% to 31%; pediatrics, 13% to 23.2%), abnormal gait (adults, 5% to 28.7%; pediatrics, 8% to 23.2%), nystagmus (adults, 2% to 26%; pediatrics, 9%), tremor (adults, 3% to 16%; pediatrics, 6%), and fatigue (adults, 5% to 21%; pediatrics, 13%) are the most frequent adverse effects observed during therapy with oral oxcarbazepine. Asthenia (adults, 3% to 6%; pediatrics, 2%), amnesia (1% to 5%), vertigo (adults, 3% to 15%; pediatrics, 2%), insomnia (2% to 6%), nervousness (2% to 7%), and confusion (7%) have also been reported (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011; Farago, 1987; Sillanpaa & Pihlaja, 1989; Houtkooper et al, 1987; Dam et al, 1989; Philbert et al, 1986; Friis et al, 1993; Pendlebury et al, 1989; Curran & Java, 1993).

a) CASE REPORT: A 13-year-old autistic boy (weight 60 kg) who was taking oxcarbazepine (300 mg twice daily) and risperidone (1 mg 3 times daily) for the management of disruptive behaviors, developed vomiting 1 hour after ingesting 250 mL (15 g; max MHD concentration 46.6 mg/L) of oxcarbazepine suspension. He presented with somnolence (minimal Glasgow Coma Scale 13), but no other symptoms were observed. Following supportive care, including activated charcoal, his symptoms gradually resolved over the next 12 hours (Pedrini et al, 2009).
b) CASE REPORT: Following an inadvertent overdose of 3300 mg over a one day period (normal dose, 2400 mg/day), a 38-year-old woman developed tinnitus, vertigo, diplopia, somnolence, and lethargy. Following admission to the ED she had a partial seizure. The patient recovered following symptomatic therapy (Jolliff et al, 2001).
c) CASE REPORT: A 36-year-old man with epilepsy developed only somnolence following the ingestion of 102 tablets of 300 mg (30,600 mg) oxcarbazepine. His vital signs were blood pressure of 155/105 and pulse of 98. Two hours after ingestion, serum levels of oxcarbazepine and MDH (10-monohydroxy derivate; the active metabolite) were 31.6 mg/L (10-fold higher than the therapeutic dosage) and 37.2 mg/L, respectively. Approximately 7 hours after ingestion, the serum levels of oxcarbazepine and MDH were 0.67 mg/L and 59 mg/L (peak level), respectively. Following supportive therapy, he recovered without further sequelae. The authors proposed that the relative low toxicity of the drug in this patient could be due to the fact that oxcarbazepine is a prodrug and that the formation of the active MHD metabolite is a rate-limiting process (van Opstal et al, 2004).

a) CASE REPORT: An 8-year-old girl with complex partial seizures and untreated ADHD developed tardive dyskinesia approximately 10 days after starting oxcarbazepine. Prior to admission, she had 2 seizures in the past month. While hospitalized, therapy was initiated with oxcarbazepine 15 mg/kg/day for 1 week, titrated to 30 mg/kg/day thereafter. After 3 days of full-dose therapy, she presented with trismus, eye deviation, protrusion of the tongue, and lateral trunk flexion. Tardive dyskinesia was diagnosed and oxcarbazepine was immediately discontinued. She was treated with a single-dose of diazepam IV and diphenhydramine orally for 2 weeks. Her symptoms resolved 3 days after oxcarbazepine was discontinued. A score of 6 on the Naranjo ADR Probability Scale showed the relationship between oxcarbazepine and occurrence of tardive dyskinesia was probable (Herguner et al, 2010).

a) Status epilepticus has been reported in several mentally-retarded epileptic patients (Sillanpaa & Pihlaja, 1989). Recovery was observed following withdrawal of the drug. This complication may have been related to the severe mental retardation in these patients. Clinically significant oxcarbazepine-induced hyponatremia may result in seizures (Johannessen & Nielson, 1987).

a) Following an inadvertent over of 3300 mg over a one day period (normal dose, 2400 mg/day), a 38-year-old female developed a witnessed partial seizure in the ED. She recovered following symptomatic therapy (Jolliff et al, 2001).

a) Metabolic encephalopathy has been reported in a patient due to oxcarbazepine-induced hyponatremia (Rosendahl & Friis, 1991).

a) Oculogyric crisis, which occurred with carbamazepine and ceased following its discontinuance, recurred following onset of therapy with oxcarbazepine in a 31-year-old man. The oculogyric crisis occurred as a dose-related event, with as many as 30 episodes daily at higher oxcarbazepine doses of 1800 mg/day. Following implantation of a vagus nerve stimulator, oculogyric crisis ceased, although oxcarbazepine therapy was continued (Gatzonis et al, 1999).

a) Nausea and vomiting have been reported in 22% and 15%, respectively, of patients in clinical trials (n=86) at the maximum dosage range of 2400 mg/day (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) CASE REPORT: A 13-year-old autistic boy (weight 60 kg) who was taking oxcarbazepine (300 mg twice daily) and risperidone (1 mg 3 times daily) for the management of disruptive behaviors, developed vomiting 1 hour after ingesting 250 mL (15 g) of oxcarbazepine suspension. He presented with somnolence (minimal Glasgow Coma Scale 13), but no other symptoms were observed. Following supportive care, including activated charcoal, his symptoms gradually resolved over the next 12 hours (Pedrini et al, 2009).

a) Diarrhea was reported in 7% of patients treated with oxcarbazepine (n=55) compared with 2% treated with placebo (n=49) in a controlled clinical trial of oxcarbazepine monotherapy among adults with no previous antiepileptic drug experience (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Abdominal pain was reported in 10%. 13%, 11%, and 5% of patients treated with adjunctive oxcarbazepine 600 mg/day (n=163), 1200 mg/day (n=171), 2400 mg/day (n=126), or placebo (n=166), respectively in a controlled clinical trial of adults with epilepsy (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Constipation was reported in 5% of patients treated with oxcarbazepine (n=55) compared with 0% treated with placebo (n=49) in a controlled clinical trial of oxcarbazepine monotherapy among adults with no previous antiepileptic drug experience (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Pancreatitis has occurred during postmarketing use of oxcarbazepine (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Elevations in serum GGT have been observed in some patients treated with oxcarbazepine or 10-hydroxy-carbazepine (Farago, 1987), although no severe hepatotoxic reactions have been reported.

a) CASE REPORT: An 8-year-old girl treated for 14 days with oxcarbazepine 10 mg/kg/day for partial seizures experienced acute hepatitis. On day 12 of therapy, she had a poor appetite and malaise. On day 13, she had a fever. Upon admission (day 14), elevated levels were observed for AST 1245 unit/L, ALT 1258 units/L, and alkaline phosphatase 128 international units/L, but total bilirubin was normal. Serology tests showed reactive IgG antibodies for hepatitis A, but IgM antibodies were nonreactive. Other viral infections (hepatitis B, C, Epstein-Barr virus, cytomegalovirus) and autoimmune reaction were ruled-out. Oxcarbazepine was switched to levetiracetam 20 mg/kg/day. Four days after discontinuing oxcarbazepine, AST and ALT levels dropped to 159 units/L and 492 units/L, respectively. The patient's signs and symptoms resolved and she was discharged in stable condition. With her serological profile and no other hepatotoxic drug history, researchers concluded that the patient's acute hepatitis stemmed from oxcarbazepine use (Hsu & Huang, 2010).

a) ADULT: A 63-year-old woman with a history of depression with psychotic features, presented with low-grade fever and thrombocytopenia (platelet count of 208,000/microL) several days after oxcarbazepine (300 mg twice daily) was added to her ongoing treatment of aripiprazole and venlafaxine. Platelet count during a previous hospitalization was 300,000/microL. Idiopathic thrombocytopenic purpura was ruled out and partial thromboplastin time, prothrombin time, and international normalized ratio were within normal limits. Platelet count continued to drop and was 18,000/microL by day 10 of treatment. Oxcarbazepine was discontinued and 4 days later, platelet count increased to 250,000/microL and was within normal limits 7 days after discontinuing oxcarbazepine (Mahmud et al, 2006).
b) ADULT: A case report described thrombocytopenia in a 63-year-old woman after being treated with oxcarbazepine. The patient, who had a history of depression with psychotic features and multiple psychiatric hospitalizations, presented to the hospital with increasingly disorganized behavior and paranoid ideation. Platelet count at time of admission was 300,000/microL. Initial treatment with nortriptyline and risperidone was unsuccessful, and the patient was switched to aripiprazole and venlafaxine. After an inadequate response, oxcarbazepine 300 mg twice daily was added to her ongoing treatment of aripiprazole and venlafaxine. The patient responded well to this, displaying an improvement in mood and energy levels. Following oxcarbazepine therapy for a few days, the patient developed a low-grade fever and platelet count dropped to 208,000/microL. Idiopathic thrombocytopenic purpura was ruled out and partial thromboplastin time, prothrombin time, and international normalized ratio were within normal limits. Platelet count continued to drop and was 18,000/microL by day 10 of treatment. Oxcarbazepine was discontinued and 4 days later, platelet count increased to 250,000/microL and was within normal limits 7 days after discontinuing oxcarbazepine (Mahmud et al, 2006).
c) PEDIATRIC: Thrombocytopenia, thrombocytopenic purpura, and leukopenia were reported in a 10-year-old boy 2 weeks after beginning oral oxcarbazepine therapy for epilepsy. The patient presented with a 3-day history of continuous fever, pinpoint petechiae on lower limbs, red pharynx, swollen tonsils and lymph nodes. He was not taking any other mediation, had no history of hematologic disease, and there were no abnormalities found in the CBC, electrolyte panel, or renal and hepatic function tests. On admission, 17 days after the initiation of oxcarbazepine (1000 mg/day), laboratory results revealed a low WBC of 2 x 10(9)/L, platelet count of 10 x 10(9)/L, and a potassium level of 3.15 mmol/L. There were high levels of C-reactive protein (11.7 mg/L; reference value, less than 8 mg/L) and immune globulin E (325 International Units/L), but there was no significant elevation of serum compliment proteins C3 or C4. The BUN was slightly increased at 6.62 mmol/L and RBCs were observed in the urine (4/microL), indicating possible kidney damage. The prothrombin time, INR, fibrinogen, and thrombin time were all within normal limits, and there was no evidence of acute infection by cytomegalovirus or Epstein Barr virus. Oxcarbazepine was continued and IV immune globulin (1 g/kg/day) was initiated resulting in an increase in the platelet count to 103 x 10(9)/L and resolution of skin petechiae. However, as leukopenia and moderate fever persisted, 5 days after admission, oxcarbazepine was discontinued and replaced by levetiracetam. Two days following the discontinuation of oxcarbazepine, the fever resolved and, by the 5th day, the potassium level and the WBC normalized. The patient's DNA was genotyped and he was found not to have the HLA-Bx1502, HLA-Bx5801, or HLA-Ax3101 genes (He et al, 2011).

a) Thrombocytopenia, thrombocytopenic purpura, and leukopenia were reported in a 10-year-old boy 2 weeks after beginning oral oxcarbazepine therapy for epilepsy. The patient presented with a 3-day history of continuous fever, pinpoint petechiae on lower limbs, red pharynx, swollen tonsils and lymph nodes. He was not taking any other mediation, had no history of hematologic disease, and there were no abnormalities found in the CBC, electrolyte panel, or renal and hepatic function tests. On admission, 17 days after the initiation of oxcarbazepine (1000 mg/day), laboratory results revealed a low WBC of 2 x 10(9)/L, platelet count of 10 x 10(9)/L, and a potassium level of 3.15 mmol/L. There were high levels of C-reactive protein (11.7 mg/L; reference value, less than 8 mg/L) and immune globulin E (325 International Units/L), but there was no significant elevation of serum compliment proteins C3 or C4. The BUN was slightly increased at 6.62 mmol/L and RBCs were observed in the urine (4/microL), indicating possible kidney damage. The prothrombin time, INR, fibrinogen, and thrombin time were all within normal limits, and there was no evidence of acute infection by cytomegalovirus or Epstein Barr virus. Oxcarbazepine was continued and IV immune globulin (1 g/kg/day) was initiated resulting in an increase in the platelet count to 103 x 10(9)/L and resolution of skin petechiae. However, as leukopenia and moderate fever persisted, 5 days after admission, oxcarbazepine was discontinued and replaced by levetiracetam. Two days following the discontinuation of oxcarbazepine, the fever resolved and, by the 5th day, the potassium level and the WBC normalized. The patient's DNA was genotyped and he was found not to have the HLA-Bx1502, HLA-Bx5801, or HLA-Ax3101 genes (He et al, 2011).

a) Hypersensitivity erythematous, itchy rashes have been reported following therapeutic doses. Rash may be associated with a mild eosinophilia (Watts & Bird, 1991). Rash was reported in 7% of patients on oxcarbazepine monotherapy in one study (Friis et al, 1993).

a) Erythema multiforme has been reported with postmarketing use of oxcarbazepine (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011)

a) CASE REPORT: Serious, sometimes life-threatening cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with the use of oxcarbazepine in children and adults. Some patients have required hospitalization, and rare cases of death have been reported. Additionally, rechallenge with the drug has resulted in recurrence of the dermatologic reactions. The rate at which these dermatologic events have been reported in association with oxcarbazepine use exceeds the rate at which these events are reported in the general population by 3- to 10-fold. The median time of onset in reported cases was 19 days (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).
b) CASE REPORT: A 9-year-old boy developed Stevens-Johnson syndrome (SJS) within 14 days of initiating oxcarbazepine (300 mg daily for 1 week and increased to 600 mg daily) for treatment of seizures. Fourteen days after beginning therapy with oxcarbazepine, the patient developed maculopapule rashes on his face and thigh along with high fever. Two days later, he developed blisters on his thigh, multiple oral ulcers and hyperemic conjunctivae. The patient was admitted to the emergency department with the diagnosis of presumed SJS. Laboratory analyses revealed leukocytosis (WBC 13,930/mcL; normal range, 4000 to 10,000/mcL), elevated C-reactive protein (50.59 mcg/mL; range, 0 to 5 mcg/mL). Human leukocyte antigen (HLA) genotyping showed HLA-Bx1518/Bx4001 and skin pathology finding revealed lymphohistiocytic infiltration around the blood vessels and scanty eosinophils, which was consistent with SJS. The patient improved with steroid and antihistamine treatment for 7 days and was discharged 12 days later. Authors concluded that similar to carbamazepine-induced SJS, the role of the HLA-B15 variant may be associated with the development of oxcarbazepine-induced SJS (Lin et al, 2009).

a) In a male reproductive study of valproate, carbamazepine and oxcarbazepine, low daily doses of oxcarbazepine were shown to have no effects on serum concentrations of reproductive hormones. Men receiving high dose oxcarbazepine had increased serum testosterone, gonadotropin, and sex hormone-binding globulin (SHBG) levels. All patient groups were reported to have significant elevated serum insulin levels (not dose dependent) (Rattya et al, 2001).

a) Hypersensitivity reactions to oxcarbazepine have occurred in 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).
b) Allergic skin reactions have been reported less frequently with oxcarbazepine as compared to carbamazepine in some clinical studies (Dam et al, 1989; Dam, 1990; Houtkooper et al, 1987). There is evidence that oxcarbazepine can be used safely as an alternative in some patients with carbamazepine induced hypersensitivity (Zakrzewska & Ivanyi, 1988; Houtkooper et al, 1987; Zakrzewska & Patsalos, 1989).

a) Rare cases of anaphylaxis have been reported in patients following initial or subsequent oxcarbazepine use (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

a) Fetal structural abnormalities and other developmental toxicities were reported in the offspring of animals treated with either oxcarbazepine or its active metabolite, 10-hydroxy metabolite (MHD), during pregnancy at doses similar to the maximum recommended human dose (MRHD). In pregnant rats treated with oxcarbazepine 30, 300, or 1000 mg/kg orally throughout organogenesis, increased embryofetal death and decreased fetal body weights were observed at the 1000-mg/kg dose (approximately 4 times the MRHD). In pregnant rabbits treated with MHD 20, 100, or 200 mg/kg during organogenesis, increased embryofetal mortality was observed at the 200-mg/kg dose (1.5 times the MRHD). In female rats treated with oxcarbazepine 25, 50, or 150 mg/kg during late gestation and during lactation, reduced body weights and altered behavior (decreased activity) were observed at the 150-mg/kg dose (0.6 times the MRHD). Rats treated with MHD 25, 75, or 250 mg/kg orally during gestation and lactation resulted in persistently reduced offspring weights at the 250-mg/kg dose (equivalent to the MRHD) (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).
b) In mice, a malformation incidence of 8% was reported when pregnant mice were given the highest tolerable oxcarbazepine dose of 1100 mg/kg/day on days 6 through 18 of gestation compared with a 5% incidence in those mice given no drugs (Bennett et al, 1996).

a) In pregnant rats treated with oxcarbazepine 30, 300, or 1000 mg/kg orally throughout organogenesis, maternal toxicity (decreased body weight gain, clinical signs) was observed at doses of 300 mg/kg or greater; however, there is no evidence to suggest that teratogenicity was secondary to the maternal effects. In pregnant rabbits treated with MHD 20, 100, or 200 mg/kg during organogenesis, only minimal maternal toxicity was observed at the 200 mg/kg dose (1.5 times the MRHD) (Prod Info TRILEPTAL(R) film-coated oral tablets, oral suspension, 2011).

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.

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).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

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.

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).

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

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).

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 .

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).

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).

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).

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):

a) BENZTROPINE: 1 to 4 mg once or twice daily intravenously or intramuscularly; maximum dose: 6 mg/day; 1 to 2 mg of the injection will usually provide quick relief in emergency situations (Prod Info benztropine mesylate IV, IM injection, 2009).
b) DIPHENHYDRAMINE: 10 to 50 mg intravenously at a rate not exceeding 25 mg/minute or deep intramuscularly; maximum dose: 100 mg/dose; 400 mg/day (Prod Info diphenhydramine hcl injection, 2006).

a) DIPHENHYDRAMINE: 5 mg/kg/day or 150 mg/m(2)/day intravenously divided into 4 doses at a rate not to exceed 25 mg/min, or deep intramuscularly; maximum dose: 300 mg/day. Not recommended in premature infants and neonates (Prod Info diphenhydramine hcl injection, 2006).

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

a) ALBUTEROL

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

a) DIPHENHYDRAMINE

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

a) EPINEPHRINE

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

a) Initially, 600 mg orally once daily; increase to 1200 to 2400 mg once daily (Prod Info OXTELLAR XR oral extended-release tablets, 2012)

a) Initial dose: 600 mg/day in 2 divided doses. The dose may be increased at weekly intervals, as clinically indicated, by a maximum of 600 mg/day to a recommended daily dose of 1200 mg/day (Prod Info Trileptal(R) oral film-coated tablets, oral suspension, 2014)

a) CONVERSION TO MONOTHERAPY: initiate treatment at 600 mg/day in 2 divided doses. Reduce the dosage of concomitantly given anticonvulsants simultaneously (should be completely withdrawn over period of 3 to 6 weeks). The dosage of oxcarbazepine can be increased by 600 mg/day on a weekly basis to a maximum of 2400 mg daily (Prod Info Trileptal(R) oral film-coated tablets, oral suspension, 2014).
b) INITIATION OF MONOTHERAPY: initiate treatment at 600 mg/day in 2 divided doses. The dose may be increased by 300 mg/day every third day to a dose of 1200 mg/day (Prod Info Trileptal(R) oral film-coated tablets, oral suspension, 2014).

a) 4 TO 16 YEARS OLD (Prod Info Trileptal(R) oral film-coated tablets, oral suspension, 2014):
b) 2 TO LESS THAN 4 YEARS OLD (Prod Info Trileptal(R) oral film-coated tablets, oral suspension, 2014):

a) 6 TO 17 YEARS OLD (Prod Info OXTELLAR XR oral extended-release tablets, 2012):

a) Initiation of monotherapy, 8 to 10 mg/kg/day orally in 2 divided doses. The dose may be increased by 5 mg/kg/day every third day.
b) Conversion to monotherapy, 8 to 10 mg/kg/day orally in 2 divided doses while simultaneously reducing the dosage of concomitantly given anticonvulsants. The dose may be increased by 10 mg/kg/day at weekly intervals.
c) Maintenance, 600 to 900 mg/day for weight of 20 kg; 900 to 1200 mg/day for 25 to 30 kg; 900 to 1500 mg/day for 35 to 40 kg; 1200 to 1500 mg/day for 45 kg; 1200 to 1800 mg/day for 50 to 55 kg; 1200 to 2100 mg/day for 60 to 70 kg.

a) A wide therapeutic serum range has been reported. In patients with trigeminal neuralgia, therapeutic serum concentrations of the active metabolite of oxcarbazepine (10-hydroxy-carbazepine) have ranged from 50 to 110 micromoles/liter (Zakrzewska & Patsalos, 1989).
b) Friis et al (1993) reported a mean trough plasma level of the active metabolite, 10-hydroxy-carbazepine (MHD), of 73 micromoles/liter (range 11 to 159 micromoles/liter) in 374 patients during oxcarbazepine monotherapy (Friis et al, 1993).
c) A mean serum concentration of the active metabolite, 10-hydroxy-carbazepine, was reported to be 57.0 micromoles/liter (S.D. +/- 20.2) in a clinical trial with mean final daily doses of 1040 milligrams (range, 300 to 1800 milligrams) (Dam et al, 1989).
d) Jolliff et al (2001) reported a normal serum therapeutic range of the active metabolite (MHD) to be 10 to 35 micrograms/milliliter (Jolliff et al, 2001).

a) CASE REPORT: A 6-hour post-ingestion serum level of the active metabolite (MHD) was reported to be 45.6 micrograms/milliliter (therapeutic range, 10 to 35 micrograms/milliliter) following an inadvertent overdose of 3300 milligrams taken over a one day period in a 38-year-old female. A serum carbamazepine level was non-detectable (Jolliff et al, 2001).
b) CASE REPORT: A 36-year-old man with epilepsy ingested 102 tablets of 300 mg (30600 mg) oxcarbazepine. Two hours after ingestion, serum levels of oxcarbazepine and MDH (10-monohydroxy derivate; the active metabolite) were 31.6 mg/L (10-fold higher than the therapeutic dosage) and 37.2 mg/L, respectively. Approximately 7 hours after ingestion, the serum levels of oxcarbazepine and MDH were 0.67 mg/L and 59 mg/L (peak level), respectively. The concentration of the inactive 10,11-dihydroxy derivative were continuing to climb slowly at 24 hours after the ingestion (van Opstal et al, 2004).

a) CASE REPORT: A 13-year-old autistic boy (weight 60 kg) who was taking oxcarbazepine (300 mg twice daily) and risperidone (1 mg 3 times daily) for the management of disruptive behaviors, developed vomiting 1 hour after ingesting 250 mL (15 g) of oxcarbazepine suspension. He presented with somnolence (minimal Glasgow Coma Scale 13), but no other symptoms were observed. Following supportive care, including activated charcoal, his symptoms gradually resolved over the next 12 hours. Oxcarbazepine and 10-monohydroxy-carbazepine (MHD) concentrations 2 hours postingestion were 7.9 mg/L and 34.5 mg/L, respectively. Oxcarbazepine concentrations 8 hours and 24 hours postingestion were 0.3 mg/L and undetectable, respectively. MHD concentration was 46.6 mg/L 8 hours postingestion and decreased gradually (Pedrini et al, 2009).
b) Serum levels of the active metabolite, 10-carboxy-carbazepine (MHD), of 35 to 40 milligrams/liter were reported to be associated with the start of adverse effects in most pediatric patients in a survey (n=46). However, levels of more than 40 milligrams/liter were tolerated in some patients, whereas adverse effects were reported at levels of 24 milligrams/liter in other patients (Borusiak et al, 1998).