Carbamazepine poisoning

INTRODUCTION — 

Carbamazepine is used for the treatment of both partial and generalized seizures, trigeminal neuralgia, and other neuropathic pain syndromes. Additionally, it is used in the treatment of bipolar disorder as a mood stabilizer.

In 2023, America's Poison Center reported 2011 toxic exposures to carbamazepine [1]. Of these, 939 were isolated ingestions, and 660 were treated in a health care facility. Forty-eight patients experienced major toxicity, defined as life-threatening or resulting in significant disability [1].

The toxicology, diagnosis, and management of acute carbamazepine poisoning are discussed here. The clinical use of carbamazepine and chronic complications related to its use are reviewed separately.

●(See "Overview of the management of epilepsy in adults".)

●(See "Seizures and epilepsy in children: Initial treatment and monitoring".)

●(See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — 

Carbamazepine interacts with multiple receptors and ion channels. Its therapeutic effect is primarily from binding to sodium channels in their inactivated state, which inhibits neuron depolarization and decreases glutamate release [2]. Carbamazepine also has anticholinergic effects, which is more relevant in overdose rather than the therapeutic setting [3]. (See "Anticholinergic poisoning".)

In carbamazepine toxicity, sodium channel blockade may manifest as cardiovascular toxicity, particularly prolongation of the QRS interval. This conduction abnormality predisposes patients to ventricular dysrhythmias and hypotension [4].

Carbamazepine appears to have a paradoxical effect on adenosine receptors. In therapeutic doses, the drug inhibits presynaptic reuptake of adenosine, resulting in modulation and inhibition of glutamate neurotransmission [5,6]. In overdose, carbamazepine antagonizes adenosine receptors, resulting in a proconvulsant effect, which explains the seizure activity commonly seen in carbamazepine toxicity [6].

KINETICS — 

Carbamazepine is available in both immediate-release and controlled-release tablets and an immediate-release oral suspension. Absorption of therapeutic doses of an immediate-release formulation occurs in 3 to 12 hours [2,7]. In overdose, absorption is erratic and may be prolonged, with peak concentrations occurring more than 96 hours after ingestion of controlled-release formulations [8]. The volume of distribution ranges from 0.8 to 1.8 L/kg, and protein binding is estimated to be between 75 and 90 percent [9].

Carbamazepine undergoes hepatic metabolism, primarily through cytochrome P450 (CYP) 3A4 [10]. More than 30 metabolites have been identified [7,11]. The most important of these are carbamazepine-10,11-epoxide, which has intrinsic anticonvulsant activity, and trans-10-11-dihydroxy-10,11-dihydrocarbamazepine, an arene oxide metabolite believed to be responsible for the hypersensitivity reactions and teratogenic effects of carbamazepine [12,13].

Carbamazepine is a CYP 3A4 substrate as well as an inducer of multiple cytochrome P450 isoenzymes and subject to a number of drug-drug interactions (table 1). Toxic concentrations of carbamazepine may result from CYP 3A4 inhibition from erythromycin, fluoxetine, and cimetidine, among numerous other drugs [2,14,15]. Conversely, CYP 3A4 inducers, such as phenytoin and phenobarbital, may decrease carbamazepine concentrations [10]. Plasma concentrations of many medications, including haloperidol and clozapine [16,17], are reduced in the setting of carbamazepine use. Carbamazepine induces its own metabolism, and dose requirements increase with chronic use [11].

Carbamazepine’s elimination half-life demonstrates significant variability with therapeutic dosing, ranging from 12 to 17 hours following chronic therapeutic use [2]. The half-life can be significantly prolonged following overdose and averages 35 hours following a single overdose and 20 hours after multiple dosages [18]. In overdose, carbamazepine’s elimination is thought to display zero-order kinetics [18,19].

CLINICAL FEATURES — 

Clinicians should consider the diagnosis of carbamazepine toxicity in any patient with cerebellar symptoms, central nervous system (CNS) depression, and signs of the anticholinergic toxidrome (table 2), particularly if the patient is known to have a seizure disorder or access to anticonvulsants.

History — Important historical information in the patient with suspected carbamazepine poisoning includes:

●Identity of any ingested pills, including dose and formulation (eg, immediate-release or controlled-release)

●Approximate number of pills ingested

●Time of ingestion

●Whether the patient takes carbamazepine or any other medication chronically

●Possible coingestants

Other helpful information includes symptoms prior to seeking medical care (such as vomiting, prolonged unconsciousness, or seizure activity) and whether any treatment was provided prior to arrival.

Examination and clinical manifestations — Carbamazepine toxicity frequently presents with neurologic, cardiovascular, and anticholinergic signs and symptoms. Patients with mild carbamazepine toxicity or those presenting shortly after the ingestion when absorption remains incomplete may demonstrate drowsiness, nystagmus, and tachycardia [8,20-24]. More severe intoxication may manifest as lethargy, seizure, coma, hypotension, or dysrhythmia [21-25]. Signs and symptoms of anticholinergic toxicity are expected. Toxicity may be prolonged due to carbamazepine's delayed and erratic absorption. (See "Anticholinergic poisoning".)

Tachycardia is common following carbamazepine overdose. Hypotension is observed in moderate to severe poisoning and may be due to direct negative inotropic effects. Hyperthermia may result from seizure activity or anticholinergic effects (impaired heat dissipation) [21,24].

Neurologic examination typically reveals altered mental status. The patient may be agitated, but CNS depression, ranging from drowsiness to coma, is more common [20-26]. Coma is often cyclical and consciousness may fluctuate abruptly from alert (although encephalopathic) to comatose [20,25]. Ataxia and dysmetria (loss of coordinated movement) are common [22,25]. Choreoathetosis or dyskinesia may be seen with therapeutic use or in overdose.

Seizures may occur, particularly in patients with underlying epilepsy [21-25]. Seizures are often self-limited but may rarely progress to status epilepticus [21,25]. Myoclonus, hypertonia, hypotonia, and choreoathetosis have all been described in the setting of acute carbamazepine toxicity [23,24,27]. A single case report has described sensorineural hearing loss [28].

Ocular examination frequently reveals nystagmus and mydriasis, and occasionally ophthalmoplegia [8,19,23,27]. Oropharyngeal examination often reveals dry mucus membranes, and may show signs of trauma, which can occur from a fall due to a depressed level of consciousness or seizure activity.

Abdominal examination may reveal hypoactive or absent bowel sounds and the urinary bladder may be palpable from urinary retention, both due to the anticholinergic effects of the drug. Abdominal tenderness and pancreatitis are rare, but have been described [29].

The skin may be hot, dry, and flushed and the axillae dry due to anticholinergic effects. One case report describes bullous eruptions following carbamazepine poisoning [30].

Chronic use of carbamazepine has been associated with leukopenia, agranulocytosis, and rarely, aplastic anemia. Other chronic side effects can include drug hypersensitivity, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients with Asian ancestry or carriers of the HLA-B*15:02 gene are at increased risk of carbamazepine-associated SJS/TEN. The US Food and Drug Administration recommends that patient populations at risk should be screened for the presence of the HLA-B*15:02 allele prior to starting carbamazepine [31]. Chronic side effects from carbamazepine therapy are discussed separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine' and "Drug hypersensitivity: Classification and clinical features" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis" and "Acquired aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis".)

DIFFERENTIAL DIAGNOSIS — 

Carbamazepine toxicity may present in a similar fashion to other poisonings as well as metabolic, infectious, or structural central nervous system (CNS) disorders.

The toxicologic differential diagnosis is based largely on the presenting symptoms. If anticholinergic toxicity is present, anticholinergic agents (eg, tricyclic antidepressants, antihistamines, phenothiazines, and cyclobenzaprine) should be considered. Cerebellar abnormalities and CNS depression should prompt consideration of sedative-hypnotic toxicity or toxic effects from other anticonvulsants, such as phenytoin, valproic acid, or topiramate. Serum drug testing may help refine the differential diagnosis. (See "Anticholinergic poisoning" and "Tricyclic antidepressant poisoning" and "Phenytoin poisoning" and "Valproic acid poisoning" and "Benzodiazepine poisoning".)

Carbon monoxide (CO) poisoning causes cardiotoxicity and neurotoxicity, which are also prominent in carbamazepine poisoning. If CO poisoning is considered in the differential diagnosis, a carboxyhemoglobin concentration should be obtained. (See "Carbon monoxide poisoning".)

CNS pathology, especially cerebellar disease, can present with findings similar to acute carbamazepine poisoning. Hypoglycemia, encephalitis-meningitis, status epilepticus, hepatic encephalopathy, subarachnoid hemorrhage, and stroke all may resemble carbamazepine toxicity. Hypoglycemia can be quickly excluded by finger-stick glucose testing. Neurologic imaging and analysis of the cerebrospinal fluid can distinguish many of these conditions from carbamazepine toxicity. (See "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, causes, and diagnosis" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis" and "Hepatic encephalopathy in adults: Clinical manifestations and diagnosis" and "Initial assessment and management of acute stroke".)

LABORATORY EVALUATION

General diagnostic testing in overdose — Routine laboratory evaluation of the poisoned patient should include the following:

●Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status

●Acetaminophen and salicylate concentrations, to rule out these common coingestions

●Pregnancy test in females of childbearing age

Serum carbamazepine concentration — Serum carbamazepine concentrations should be followed serially in an acute overdose. Serum concentrations may not peak for over 96 hours; concentrations should be obtained every four to six hours until there is a definite downward trend and the patient is improving clinically [8]. Therapeutic concentrations of carbamazepine range from 4 to 12 mcg/mL (17 to 51 micromol/L).

The relationship between carbamazepine concentrations and particular toxicities varies. Carbamazepine concentrations above 40 mcg/mL (170 micromol/L) correlate with an increased risk for seizures, apnea, dystonia, hypotension, and coma [22,25,27,32]. The relationship between the serum carbamazepine concentration and seizure risk is less consistent, but one small retrospective case series reported that seizures occurred exclusively in patients with epilepsy and with a serum carbamazepine concentration greater than 25 mcg/mL [32].

Oxcarbazepine can produce a false positive result with both serum carbamazepine immunoassay testing and gas chromatography/mass spectrometry. Oxcarbazepine is not metabolized to carbamazepine in vivo [33]. It is likely that a structurally similar or a common metabolite (10,11-dihydroxycarbamazepine) causes this interference. It is unclear if such interference occurs only following overdose of oxcarbazepine or if it is possible after therapeutic use.

Ancillary testing — Severe carbamazepine toxicity can cause QRS prolongation and dysrhythmias. Patients should be placed on continuous cardiac monitoring and a 12-lead electrocardiogram (ECG) should be obtained. Should QRS prolongation develop, sodium bicarbonate should be administered and a repeat ECG obtained. (See 'QRS interval prolongation' below.)

Sinus tachycardia is the most frequently observed cardiac effect of carbamazepine, but bradycardia, atrioventricular block, premature ventricular contractions, ventricular tachycardia, and junctional escape rhythms have all been attributed to carbamazepine toxicity [25].

Rhabdomyolysis may develop in an acute overdose of carbamazepine, if the patient has seized or experienced a prolonged period of unconsciousness. Creatine phosphokinase should be obtained initially and followed serially if elevated or if the history suggests the patient is at risk for rhabdomyolysis. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)

Imaging is not routinely needed following carbamazepine ingestion; however, it may be required if concomitant pathology is suspected or if the diagnosis is in question. As an example, computed tomography of the head is indicated if the patient is encephalopathic or has signs of head trauma. Also, if history or examination suggests aspiration or pulmonary edema, a chest radiograph should be obtained.

If urine toxicology testing is performed, carbamazepine may trigger a false positive result for tricyclic antidepressants on immunoassay because of structural similarities among these drugs [34-36].

Laboratory tests may reveal evidence of chronic toxicity. Examples include leukopenia, or rarely agranulocytosis, on a complete blood count [37], or hyponatremia on a basic metabolic profile [38]. Liver function tests (LFTs) are elevated in up to 30 percent of patients using carbamazepine chronically [20,39]. Hyperammonemia, although more common with valproic acid toxicity, has been reported in carbamazepine poisoning [40-42]. (See "Valproic acid poisoning", section on 'Hyperammonemia'.)

MANAGEMENT

Airway, breathing, and circulation — Patients with significant central nervous system (CNS) depression may lose protective airway reflexes and should be tracheally intubated, particularly in light of their lower seizure threshold. Short-acting neuromuscular blocking agents (eg, succinylcholine) are preferable, so as not to mask subsequent seizure activity. Induction agents with gamma-amino butyric acid (GABA) agonist activity (eg, midazolam) may be preferable depending upon the patient’s hemodynamic status.

Hypotension is initially treated with isotonic crystalloid. Caution should be exercised in patients at risk for volume overload, such as those with underlying heart disease or carbamazepine-induced myocardial dysfunction. Direct-acting vasopressors (eg, norepinephrine) are used if intravenous (IV) fluids fail to correct the hypotension.

QRS interval prolongation — Sodium channel blockade produces QRS interval prolongation and resultant ventricular dysrhythmias [43,44]. QRS prolongation due to carbamazepine toxicity is treated with sodium bicarbonate. A clear treatment threshold based upon the QRS duration has not been established; however, a reasonable practice is to give a bolus of 100 to 150 mEq of sodium bicarbonate IV for QRS intervals longer than 110 milliseconds, or in patients with hypotension. Repeat boluses may be required. Treatment of drug-induced QRS prolongation with sodium bicarbonate is described in detail separately. (See "Tricyclic antidepressant poisoning", section on 'Sodium bicarbonate for cardiac toxicity'.)

Class 1A (eg, procainamide) and 1C (eg, flecainide) antiarrhythmics should be avoided in patients with acute carbamazepine poisoning, although no studies have documented adverse effects from such treatment.

Seizures — Seizures caused by carbamazepine overdose should be treated with GABA agonists, such as benzodiazepines (eg, diazepam) or barbiturates (eg, phenobarbital). Propofol administered as a continuous infusion for the sedation of tracheally intubated patients also functions as an effective anticonvulsant, although its negative inotropic effects may limit dosing in the setting of carbamazepine cardiotoxicity (eg, hypotension, QRS prolongation). There is no role for phenytoin [45]. Electroencephalogram monitoring may be necessary in some patients. (See "Convulsive status epilepticus in adults: Management".)

Gastrointestinal decontamination

Single-dose activated charcoal — Activated charcoal (AC) remains the most common method of gastrointestinal (GI) decontamination for acute carbamazepine poisoning, although its effectiveness in improving clinical outcomes has not been proven [46]. The role of GI decontamination in the management of acute overdose is discussed separately. (See "Gastrointestinal decontamination of the poisoned patient".)

It is acceptable to give a single dose of AC (1 g/kg; maximum dose 50 g) to patients with a normal mental status who present within one to two hours of an acute overdose and are able to protect their airway [47,48]. AC should be withheld in spontaneously breathing patients with CNS sedation who may not be able to protect their airway. Tracheal intubation should not be performed solely for the purpose of giving AC.

Multidose activated charcoal — Multidose activated charcoal (MDAC; scheduled administration of more than two doses of AC) in the treatment of carbamazepine toxicity is not empirically recommended. There is little evidence that MDAC improves outcomes, although both the American Academy of Clinical Toxicologists and the European Association of Poisons Centres and Clinical Toxicologists recommend that treatment with MDAC be "considered" following carbamazepine ingestions with serious or life-threatening signs and symptoms [46,49-52]. The anticholinergic effects of carbamazepine cause decreased bowel motility and predispose patients to the development of an ileus, which often precludes MDAC therapy. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Multidose activated charcoal'.)

However, in the case of worsening clinical signs and symptoms of carbamazepine toxicity, a second dose of AC may be given to patients who are not experiencing decreased intestinal motility and are not at risk for aspiration. Evidence of decreased intestinal motility on physical examination includes decreased bowel sounds and abdominal distention, or on imaging studies includes dilated loops of bowel with air-fluid levels. Care should always be taken to ascertain normal intestinal motility prior to administering AC. It is the authors’ opinion that the benefits of MDAC do not outweigh the risks in the setting of decreased GI motility and depressed level of consciousness occurring in severe carbamazepine toxicity [46,49-52]. Administration of activated charcoal beyond the initial dose should be given in consultation with a medical toxicologist or poison center. (See 'Regional poison centers' below.)

Other methods — There is no role for other types of GI decontamination for acute carbamazepine poisoning. Whole bowel irrigation after ingestion of sustained-release tablets failed to reduce absorption in several reported cases [8,53,54], and its use is not recommended, nor is gastric emptying (by syrup of ipecac or gastric lavage) [55,56].

Extracorporeal elimination — Extracorporeal removal of carbamazepine is reserved for severely poisoned patients who continue to deteriorate (manifesting signs such as multiple refractory seizures, hemodynamic instability requiring vasopressors, or life-threatening dysrhythmias) despite maximum supportive care [57]. Decisions regarding hemodialysis in the setting of carbamazepine intoxication should be made, whenever possible, in conjunction with a medical toxicologist. (See 'Additional resources' below.)

It remains questionable whether hemodialysis and related techniques enhance the elimination of carbamazepine. At therapeutic concentrations, carbamazepine is highly protein bound, limiting the effectiveness of extracorporeal elimination.

When extracorporeal elimination is used, high-flux hemodialysis is the preferred approach. The clearance rate for hemodialysis is superior to continuous venovenous hemodialysis (CVVHD), but the technique may not be feasible in hemodynamically unstable patients and the effect on clinical outcome remains unknown [58,59]. Data regarding clearance rates for CVVHD with or without albumin dialysate are underwhelming.

Charcoal hemoperfusion can be effective but may not be readily available [8,60-64], and the procedure entails risks (eg, thrombocytopenia, coagulopathy, hypothermia, hypocalcemia, hypophosphatemia, and hypoglycemia) [61-64]. In a small retrospective study, patients managed with early charcoal hemoperfusion experienced lower peak carbamazepine concentrations, fewer cases of respiratory depression, fewer seizures, and shorter hospitalizations compared with patients not treated with extracorporeal elimination [65]. Plasmapheresis and plasma exchange have been used to enhance carbamazepine elimination [66], but outcome data are limited and use of these techniques cannot be recommended, pending further study. (See "Continuous kidney replacement therapy in acute kidney injury", section on 'Definition of CKRT modality'.)

Despite substantial improvement in hemodialysis and continuous kidney replacement therapy (CKRT) technology, most of the evidence supporting extracorporeal elimination of carbamazepine in the setting of overdose remains limited to case reports and case series [58-60,67-71]. Many of these reports use serum carbamazepine concentrations before and after hemodialysis or CKRT to gauge effectiveness, but this approach can be misleading. To judge carbamazepine clearance accurately, the concentration of carbamazepine in the dialysate should be measured. In addition, some authors hypothesize that the active metabolite carbamazepine-10,11 epoxide (CBZ–E), with its lower degree of protein binding, can be effectively cleared via extracorporeal modalities thereby limiting toxicity. However, quantitative concentrations of this metabolite are rarely measured.

Other complications

●Anticholinergic delirium — Use of physostigmine to treat patients with anticholinergic (ie, antimuscarinic) effects from acute carbamazepine toxicity is not recommended. Physostigmine’s half-life is significantly shorter than carbamazepine’s, and its therapeutic effects are transient compared with carbamazepine toxicity. Moreover, carbamazepine’s toxicity is not due solely to anticholinergic effects [72]. Potential adverse effects of physostigmine, including seizures and cardiotoxicity, further limit its utility in the setting of carbamazepine toxicity (eg, carbamazepine-induced seizures, QRS prolongation). Rivastigmine, a centrally-acting cholinesterase inhibitor that has been used to treat anticholinergic delirium, is also not recommended for carbamazepine toxicity. The use of physostigmine or rivastigmine for anticholinergic poisoning is discussed separately. (See "Anticholinergic poisoning", section on 'Antidotal therapy with physostigmine for severe toxicity'.)

●Rhabdomyolysis – This requires aggressive hydration with intravenous fluids. (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)

●Aspiration pneumonia – Aspiration may warrant antibiotic therapy; mechanical ventilation may be necessary for respiratory failure. (See "Aspiration pneumonia in adults".)

●Hyponatremia – This may require urgent correction depending upon the rate and degree of the fall in the serum sodium concentration. (See "Overview of the treatment of hyponatremia in adults".)

PEDIATRIC CONSIDERATIONS — 

Of the carbamazepine exposures reported in 2023, 146 involved children less than 20 years old. Approximately half of these were in patients under six years old [1].

Most pediatric ingestions produce only mild toxicity due to their accidental nature, and are characterized by ataxia, nystagmus, drowsiness, and emesis [19,27,73,74]. Peripheral anticholinergic signs are frequently absent [27,73]. The serum carbamazepine concentration at which more severe manifestations of toxicity develop is estimated to be lower than that of adults [27,74]. According to one case series, children with a serum carbamazepine concentration above 28 mcg/mL (117 micromol/L) are at highest risk of coma and apnea [27].

ADDITIONAL RESOURCES

Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Pharmacology – Carbamazepine binds to sodium channels in their inactivated state, inhibiting neuron depolarization and decreasing glutamate release. It is also anticholinergic (ie, antimuscarinic) and antagonizes adenosine receptors in overdose, resulting in a proconvulsant effect. Toxicity may be prolonged due to carbamazepine’s delayed and erratic absorption. (See 'Pharmacology and cellular toxicology' above and 'Kinetics' above.)

●History – Important historical information in the patient with suspected carbamazepine poisoning includes (see 'History' above):

•Identity of any ingested pills, including dose and formulation (eg, immediate release or controlled release)

•Time of ingestion

•Whether the patient takes carbamazepine or any other medication chronically

•Possible coingestants

●Clinical features – Carbamazepine toxicity frequently presents with neurologic and cardiovascular symptoms. (See 'Examination and clinical manifestations' above.)

•Patients with mild carbamazepine toxicity, or those presenting shortly after ingestion, may demonstrate signs such as drowsiness, nystagmus, and tachycardia. After acute overdose, tachycardia is common.

•Severe intoxication may manifest as lethargy, seizure, coma, hypotension, or dysrhythmia. Signs and symptoms of anticholinergic toxicity are expected.

•Sodium channel blockade from carbamazepine overdose may cause QRS prolongation and predispose to ventricular dysrhythmias.

•Hyperthermia may result from anticholinergic effects or seizure activity.

•The patient may be agitated, but central nervous system (CNS) depression, ranging from drowsiness to coma, is more common. Fluctuations in consciousness are classically encountered in carbamazepine toxicity.

●Laboratory evaluation – Serum carbamazepine concentrations should be followed serially in an acute overdose. Concentrations may not peak for a few days; concentrations should be obtained every four to six hours until there is a definite downward trend and the patient is improving clinically. Other useful diagnostic tests include fingerstick glucose, acetaminophen and salicylate concentrations, blood count, serum electrolytes, creatine phosphokinase, liver function tests, pregnancy test, and an electrocardiogram. (See 'Laboratory evaluation' above.)

●Management

•Airway control – Patients with significant CNS depression may lose protective airway reflexes and should be tracheally intubated. Short-acting neuromuscular blocking agents are preferable so as not to mask subsequent seizure activity. Induction agents with antiepileptic effects (eg, midazolam) may be preferable depending upon the patient’s hemodynamic status. (See 'Airway, breathing, and circulation' above.)

•Hypotension – Hypotension is treated initially with intravenous (IV) boluses of isotonic crystalloid. Direct-acting vasopressors (eg, norepinephrine) are used if IV fluids fail to correct the hypotension and sodium bicarbonate should be used if hypotension is due to sodium channel blockade (QRS prolongation). (See 'Airway, breathing, and circulation' above and 'QRS interval prolongation' above.)

•QRS prolongation – In a patient with QRS prolongation caused by carbamazepine overdose (ie, sodium channel blockade), we suggest treating with sodium bicarbonate (Grade 2C). A reasonable approach is to give boluses of 100 to 150 mEq of sodium bicarbonate IV for QRS intervals >110 milliseconds. (See 'QRS interval prolongation' above.)

•Seizure – In a patient who has a seizure after a carbamazepine overdose, we suggest treating with gamma-amino butyric acid (GABA) agonists such as benzodiazepines (eg, diazepam) instead of phenytoin or other anticonvulsants (Grade 2C).

•Gastrointestinal decontamination – It is acceptable to give a single dose of activated charcoal (AC; 1 g/kg; maximum dose 50 g) to patients with a normal mental status who present within one to two hours of an acute carbamazepine overdose and can protect their airway. AC should be withheld in patients with CNS depression and an unsecured airway. Tracheal intubation is not recommend solely for the purpose of giving charcoal. (See 'Gastrointestinal decontamination' above.)

•Extracorporeal elimination – Extracorporeal removal of carbamazepine with hemodialysis can be used in severely poisoned patients with signs of continued deterioration (eg, refractory seizures; hemodynamic instability requiring vasopressors; life-threatening dysrhythmias) despite maximum supportive care. Decisions regarding hemodialysis in the setting of carbamazepine intoxication should be made, whenever possible, in conjunction with a medical toxicologist. (See 'Extracorporeal elimination' above.)