eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Carbamazepine

Nidhi Kapoor, MD, Emergency Physician, Clinical Assistant Professor Emergency Medicine, Brown Medical School, Department of Emergency Medicine, Brown University School of Medicine
Richard J Hamilton, MD, FAAEM, FACMT, Chairman, Department of Emergency Medicine, Drexel University College of Medicine

Updated: Aug 14, 2008

Introduction

Background

Carbamazepine (5H-dibenzazepine-5-carboxamide) is an iminostilbene derivative with a tricyclic structure. It is an antiepileptic drug widely used for treatment of simple and complex partial seizures, trigeminal neuralgia, and bipolar affective disorder.

Carbamazepine selectively inhibits high frequency epileptic foci while normal neuronal activity remains undisturbed. Carbamazepine is absorbed erratically after oral administration because of its lipophilic nature. It has a large volume of distribution; peak plasma levels occur 4-8 hours postingestion but may take up to 24 hours to peak. The primary site of metabolism is the liver; its metabolite also is active, which may increase duration of the symptoms of toxicity.

Pathophysiology

Carbamazepine reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potentials in the epileptic focus. Carbamazepine is absorbed slowly and distributed erratically following oral administration. It enters the brain rapidly because of its high lipid solubility.

Carbamazepine is metabolized primarily in the liver by oxidative enzymes, then is conjugated with glucuronic acid, and finally is excreted in the urine. Its metabolite, carbamazepine-10,11-epoxide, is active and may achieve up to 50% concentration of the parent compound.

The elimination of carbamazepine increases over the first few weeks because of autoinduction. Carbamazepine also enhances the metabolism of phenytoin, causing its levels to fall. Erythromycin, isoniazid, and propoxyphene inhibit the hepatic metabolism of carbamazepine; therefore, the dose of carbamazepine may need to be adjusted in patients taking multiple medications.

Carbamazepine induces the hepatic cytochrome P-450 system and its half-life decreases with chronic administration. The enhanced cytochrome P-450 system increases metabolism of other antiepileptic drugs.

Frequency

United States

According to the annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System, an average of 6295 people were exposed to carbamazepine each year from 1993-1996. The total number of people exposed to carbamazepine during this period was 25,183; however, only 16,703 people (66.3%) sought treatment in a health care facility.

Mortality/Morbidity

Of the total US exposures reported to the American Association of Poison Control Centers from 1993-1996, 6359 (25.3%) resulted in no significant outcome and 1060 (4.2%) had a significant consequence. A total of 37 deaths (<1%) occurred following exposure to carbamazepine during the 4 years studied.

• Montgomery et al reports that severity at the time of initial contact with the poison control center correlates with outcome severity for children and adults.¹ However, the amount of time between ingestion and poison control center contact did not alter the correlation between initial severity and final severity.
• Far more exposures to the drug are unintentional (57.2%) than intentional (37.6%). A small number of people experienced the effects of toxicity secondary to adverse reactions rather than true poisonings (4.0%). Montgomery et al found that the reason for ingestion was correlated significantly with outcome. Carbamazepine levels greater than 85 mg/L were associated with severe toxicity.¹
• The new drug oxcarbazepine is metabolized to a product called 10-monohydrate derivate (MHD); this is the pharmacologically effective compound. van Optstal et al reported a case when a patient ingested more than 100 tablets of oxcarbazepine.² The serum level of the parent compound was 10-fold higher than the therapeutic dosage of 31.6 mg/L. However, the concentration of MHD was only 2-fold higher. MHD levels peaked 7 hours after intake. The patient survived without an adverse outcome. The authors concluded that since oxcarbazepine is a prodrug, formation of the active MHD metabolite is a rate-limiting process contributing to low overall toxicity of this drug.

Age

Roughly one third of carbamazepine exposures occur in children younger than 6 years. Pediatric patients with carbamazepine ingestion are at higher risk for dystonic reactions, coma, and apnea if serum levels exceed 28 mg/L. Children eliminate the drug more rapidly than adults.

Clinical

History

Query about whether the patient has been taking carbamazepine on an acute or chronic basis, the time of ingestion, and the approximate dose ingested.

• Drowsiness
• Slurred speech
• Ataxia
• Hallucinations
• Nausea, vomiting
• Tremors
• Seizures
• Oliguria
• Blurred vision
• Bullous skin formations

Physical

• Ocular
  • Mydriasis
  • Nystagmus
  • Ophthalmoplegia
• Hypotension
• Neurologic
  • Ataxia
  • Slurred speech
  • Dystonia, myoclonic activity
  • Varying degrees of CNS depression progressing to coma
  • Seizures, headache, confusion, and athetosis
  • Increased or decreased deep tendon reflexes
• Respiratory depression, apnea
• Delayed gastric emptying, abdominal pain
• Oliguria, urinary retention
• Skin
  • Bullous skin eruptions: Toxic epidermal necrolysis (TEN) has been reported with use of this drug. Severe drug eruptions are rare, and life-threatening events occur in 4 per million persons a year. TEN can trigger a life-threatening systemic inflammatory reaction leading to respiratory failure.³
  • Rash, dermatitis: Drug rash with eosinophilia and systemic symptoms, also known as DRESS syndrome, reflects a serious hypersensitivity reaction to drugs. Clinically, a diffuse maculopapular rash, exfoliative dermatitis, facial edema, lymphadenopathy, fever, and multivisceral involvement may be observed. All of these symptoms are associated with a high mortality rate.⁴ A cross-reactivity between carbamazepine and phenytoin occurs, which may lead to or worsen DRESS syndrome. Discontinuation of the anticonvulsants and topical steroids should ameliorate the rash.
  • Stevens-Johnson syndrome
• Blood dyscrasias
  • Pancytopenia
  • Splenomegaly
  • Lymphadenopathy
  • Vasculitis
  • Aplastic anemia
  • Agranulocytosis

Causes

• Carbamazepine toxicity may result from acute overdose or chronic therapy.
• Therapeutic levels are 4-12 mg/L, but individual variation exists.
• Patients on multiple anticonvulsants may not tolerate high levels and can be maintained at 4-8 mg/L, while others can achieve levels of 8-12 mg/L without adverse effects.
• Ataxia and nystagmus may occur at levels greater than 10 mg/L.
• Cardiovascular effects are usually seen at levels greater than 12 mg/L. The drug interferes with action potentials in Purkinje fibers and the His bundle, which may lead to atrioventricular blocks and arrhythmias.
• Peak serum levels with controlled release formulations of carbamazepine can result in delayed presentations of toxicity. Levels may not peak for 96 hours from the time of ingestion. Continuing repeat dosing of activated charcoal and whole bowel irrigation is important. Hemoperfusion may be necessary if end-organ toxicity becomes evident.
• Drug-drug interactions are known to occur. Vander et al reported a case of carbamazepine toxicity that occurred after administration of oxybutynin and an increase in the dose of dantrolene.⁵ The combination of these drugs elevated the level of carbamazepine leading to toxicity.

Differential Diagnoses

Other Problems to Be Considered

Hypersensitivity reactions (eg, dermatitis, eosinophilia, lymphadenopathy, vasculitis, splenomegaly)
Pancytopenia (eg, aplastic anemia, leukopenia)
Drug-drug interactions

Workup

Laboratory Studies

• Obtain a fingerstick glucose measurement for possible explanation of altered mental status.
• Measure carbamazepine plasma level to verify that carbamazepine toxicity is present.
• Perform liver function tests to ascertain if liver damage has occurred.
• Obtain a complete blood count with differential.
• Measure electrolyte levels; hyponatremia is not uncommon with chronic dosing but rarely is noted in acute overdose.
• Perform blood urea nitrogen and creatinine tests to ascertain if renal damage has occurred.
• Measure arterial blood gas if pulse oximetry reads less than 90-95% or if any respiratory compromise is evident.
• Obtain a pregnancy test in females of childbearing age.

Imaging Studies

• Obtain an abdominal radiograph because patients with rising serum levels may have a bezoar of undigested tablets that may be visualized radiographically.
• Obtain a chest x-ray if crackles or rales are heard on physical examination and pulmonary edema is suspected or to confirm endotracheal (ET) placement if respiratory depression occurs.

Other Tests

• Obtain a 12-lead electrocardiogram (ECG) to determine any conduction abnormalities or interval prolongations.
  • QRS widening
  • Sinus tachycardia
  • Varying degrees of atrioventricular block
  • QT prolongation

Procedures

• Repeat doses of activated charcoal and whole bowel irrigation

Treatment

Prehospital Care

• Intravenous heplock, cardiac monitor
• Intravenous fluids if patient is hypotensive

Emergency Department Care

For carbamazepine toxicity, the following ED care may be indicated:

• Place patient on a monitor.
• Administer IV fluids as needed for hypotension.
• Administer IV diazepam (5-10 mg, repeat q10-15min prn) or other suitable benzodiazepine to control seizures.
• Gastric lavage may be helpful if performed within 1 hour of ingestion.
• Protect airway by placing the patient in left lateral decubitus position or by intubating.
• Induction of emesis is not recommended because of the risk of CNS depression and seizures.
• Administer 3-4 doses of activated charcoal (1 g/kg) to enhance total body clearance and elimination.
• A saline cathartic or sorbitol may be given with the first dose of charcoal, although evidence for their effectiveness is lacking.
• Do not repeat activated charcoal administration if an ileus is present.

Consultations

• Consult a medical toxicologist or a certified poison control center.
• Nephrology consultation is indicated if considering charcoal hemoperfusion. Hemodialysis and peritoneal dialysis are not useful.

Medication

Unfortunately, no regimen is reported to be highly effective in slowing or reversing motor or cognitive symptoms of this disease. Medications for Parkinson disease, including anticholinergics, levodopa, and dopamine agonists, can reduce the rigidity to a minor extent in some patients and usually are tried at some point in the course of the disease.

Dopaminergic medications

Stimulate dopamine receptors.

Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.

Levodopa/carbidopa (Sinemet)

Unresponsiveness to this medication supports diagnosis of CBGD; thus, an empiric trial, titrated to high dose (many advocate minimum 4 g daily), is recommended for every patient.

Dosing

Adult

10/100 PO tid, increase over 2 wk to 25/250 PO tid, then increase by 25/250 q3-4d or weekly until change in motor symptoms or dose of 4 tab 25/250 tid is reached without any response

Pediatric

Not established

Interactions

Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects; antacids and MAOIs increase toxicity

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Nausea and GI complaints common; can be lessened by taking with food but avoid taking with protein; cannot discontinue abruptly; certain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in history of myocardial infarction, arrhythmias, asthma, or peptic ulcer disease; sudden discontinuation of levodopa may cause worsening of Parkinson disease; high-protein diets should be distributed throughout day to avoid fluctuations in levodopa absorption

Bromocriptine (Parlodel)

Semisynthetic ergot alkaloid derivative, strong dopamine D2-receptor agonist, partial dopamine D1-receptor agonist. Stimulates dopamine receptors in corpus striatum.
Approximately 28% absorbed from GI tract and metabolized in liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine.
Initiate at low dosage; slowly increase dosage to individualize therapy. Maintain levodopa dosage during introductory period.
Assess dosage titration every 2 wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.

Dosing

Adult

2.5 mg PO bid initially, increase to 15-20 mg bid; usually not helpful

Pediatric

Not established

Interactions

Ergot alkaloids may increase toxicity; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects

Contraindications

Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic disease

Pergolide (Permax)

Withdrawn from US market March 29, 2007. Believed to exert therapeutic effect by directly stimulating postsynaptic dopamine receptors in nigrostriatal system. Usually administered in divided doses tid. During dosage titration, dosage of concurrent levodopa/carbidopa may be decreased cautiously.

Dosing

Adult

0.05 mg PO qd initially; gradually increase to 1 mg PO tid

Pediatric

Not established

Interactions

Dopamine antagonists such as neuroleptics, phenothiazines, butyrophenones, thioxanthenes, or metoclopramide may diminish effectiveness; because pergolide mesylate is more than 90% bound to plasma proteins, exercise caution if coadministered with other drugs known to affect protein binding

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiac dysrhythmias; may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia; do not discontinue abruptly

Ropinirole (Requip)

Often not helpful but a trial probably worthwhile for patients with disabling rigidity.

Dosing

Adult

0.25 mg PO tid, gradually increase over 1 wk to 1 mg PO tid

Pediatric

Not established

Interactions

Estrogens may reduce clearance by 36%; dose adjustment may be required if estrogen therapy stopped or started during treatment with ropinirole
Potential exists for substrates or inhibitors of CYP1A2 to alter clearance; if therapy with potent CYP1A2 inhibitor stopped or started during treatment, dose adjustments may be necessary
Dopamine antagonists such as phenothiazines, butyrophenones, thioxanthenes, and metoclopramide may diminish effectiveness

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for signs and symptoms of orthostatic hypotension; dopamine receptor agonists may potentiate dopaminergic adverse effects of levodopa and may cause or exacerbate preexisting dyskinesia (decreasing dose of levodopa may ameliorate this adverse effect); retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, or pleural thickening have occurred in some patients treated with ergot-derived dopaminergic agents; complete resolution of these complications does not always occur when drug discontinued; because CNS depressants may cause possible additive sedative effects, use caution; cases of rhabdomyolysis have been reported in patients with advanced Parkinson disease treated with pramipexole

Pramipexole (Mirapex)

Nonergot dopamine agonist with specificity to D2 dopamine receptor but has also been shown to bind to D3 and D4 receptors and may stimulate dopamine activity on nerves of striatum and substantia nigra. Often not very helpful but trial worthwhile.

Dosing

Adult

0.125 mg PO tid, gradually increase over wk to 1 mg PO tid

Pediatric

Not established

Interactions

Cimetidine may increase toxicity; may increase levodopa levels

Contraindications

Documented hypersensitivity; orthostatic hypotension (can exacerbate)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal insufficiency and preexisting dyskinesias

Amantadine (Symmetrel)

Unknown mechanism of action; may release dopamine from dopaminergic terminals.

Dosing

Adult

100 mg PO bid

Pediatric

Not established

Interactions

Drugs with anticholinergic or CNS stimulant activity increase toxicity; hydrochlorothiazide plus triamterene may increase plasma concentrations

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, concomitant CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not discontinue this medication abruptly

Neuroprotective agents

No studies demonstrate that therapy with neuroprotective drugs slows the course of CBGD. However, such therapy does affect the course of other neurodegenerative dementias; therefore, neuroprotective agents are generally offered empirically.

Vitamin E (Vitec, Aquasol E)

Protects polyunsaturated fatty acids in membranes from attack by free radicals.

Dosing

Adult

1000 IU PO bid

Pediatric

Not established

Interactions

Mineral oil decreases absorption; delays absorption of iron and increases effects of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

Precautions

Although evidence of interaction with warfarin is sparse, patients on warfarin or antiplatelet agents (and families of such patients) should be instructed on risk of bleeding; start at 800 IU daily in these patients, increasing periodically while following INR, up to 1000 IU bid

Nonsteroidal anti-inflammatory agents (NSAIDS)

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Ibuprofen (Motrin, Advil)

Numerous studies suggest neuroprotective effect in preventing or slowing course of dementia of Alzheimer type.

Dosing

Adult

Not established; 200 mg PO qd advised

Pediatric

Not established

Interactions

Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely in patients taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, or decreased renal or hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Steroid hormones

Have hemodynamic effects.

Estrogens (Premarin, Cenestin)

Mode of action unclear. May act to increase cerebral circulation; may have effect on neurotransmitter systems. Slowed course of Parkinson disease has been reported in retrospective study.

Dosing

Adult

Not established, decided by primary care physician

Pediatric

Not established

Interactions

May reduce hypoprothrombinemic effect of anticoagulants; barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce levels; estrogen-induced inactivation of hepatic P-450 enzyme may reduce pharmacologic and toxicologic effects of corticosteroids; with hydantoins, may cause loss of seizure control

Contraindications

Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy)

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; may cause some degree of fluid retention (exercise caution); prolonged unopposed therapy may increase risk of endometrial hyperplasia

Benzodiazepines

By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)

Reduced disabling myoclonus in 23% patients in one trial. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.

Dosing

Adult

0.5 mg PO qd, increase to 1-1.5 mg/d in divided doses

Pediatric

Not established

Interactions

Phenytoin and barbiturates may reduce effects; CNS depressants increase toxicity

Contraindications

Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of medication

Toxins

Botulinum toxin can inhibit transmission of impulses in neuromuscular tissue.

Botulinum toxin type A (BOTOX®)

Useful in reducing excessive, abnormal muscular contractions. Binds to receptor sites on motor nerve terminals and after uptake inhibits release of acetylcholine, blocking transmission of impulses in neuromuscular tissue.
Re-examine patients 7-14 d after administering initial dose to assess for satisfactory response.
Increase doses 2-fold over previously administered dose for patients who experience incomplete paralysis of target muscle. Doses of 200-300 U usually administered; maximum safe dose believed to be 400 U.

Dosing

Adult

Initial dosing: depending on size of muscle, 25-100 U of BOTOX® per muscle are injected into abnormally contracting muscles via hollow electromyographic needle

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Aminoglycosides or drugs that interfere with neuromuscular transmission may potentiate effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not exceed recommended dosages and frequencies of administration; presence of antibodies to botulinum toxin type A may reduce effects of therapy

Follow-up

Further Inpatient Care

• Monitor carbamazepine plasma levels to make sure that they are decreasing and correlating with the clinical picture.

Transfer

• Transfer the patient if appropriate monitoring facilities or critical care areas are not available.

Deterrence/Prevention

• Education and communication between the primary care physician and the patient is important for prevention of carbamazepine overdose.

Complications

• Coma
• Stevens-Johnson syndrome
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Elevated liver function tests
• Pulmonary edema
• Pancytopenia
• Anuria

Prognosis

• The patient may experience altered levels of consciousness for several days following acute overdose.
• The patient's clinical examinations should improve as the plasma levels of the drug fall.

Patient Education

• Carefully explain the proper method of taking anticonvulsants to avoid adverse reactions.
• Educate to keep all medications and poisons in a locked cabinet or on high shelves to prevent pediatric accidental ingestions.
• Instruct patients and parents to ensure that suspensions of Tegretol be agitated vigorously before administration. Otherwise, the drug settles in its container and early doses will contain less Tegretol and subsequent underdosing will occur; later doses may contain more drug and lead to toxicity.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

Miscellaneous

Medicolegal Pitfalls

• The physician should identify and diagnose carbamazepine toxicity to prevent increased morbidity and mortality of the patient.

References

1. Montgomery VL, Richman BJ, Goldsmith LJ, Rodgers GC Jr. Severity and carbamazepine level at time of initial poison center contact correlate with outcome in carbamazepine poisoning. J Toxicol Clin Toxicol. 1995;33(4):311-23. [Medline].

2. van Opstal JM, Janknegt R, Cilissen J, et al. Severe overdosage with the antiepileptic drug oxcarbazepine. Br J Clin Pharmacol. Sep 2004;58(3):329-31. [Medline].

3. Fischer M, Hamm H, Wirbelauer J. [Severe drug-related skin reaction: toxic epidermal necrolysis caused by carbamazepine]. Klin Padiatr. Sep-Oct 2004;216(5):288-93. [Medline].

4. Allam JP, Paus T, Reichel C, et al. DRESS syndrome associated with carbamazepine and phenytoin. Eur J Dermatol. Sep-Oct 2004;14(5):339-42. [Medline].

5. Vander T, Odi H, Bluvstein V, Ronen J, Catz A. Carbamazepine toxicity following Oxybutynin and Dantrolene administration: a case report. Spinal Cord. Apr 2005;43(4):252-5. [Medline].

6. Apfelbaum JD, Caravati EM, Kerns WP, et al. Cardiovascular effects of carbamazepine toxicity. Ann Emerg Med. May 1995;25(5):631-5. [Medline].

7. Bass J, Miles MV, Tennison MB, et al. Effects of enteral tube feeding on the absorption and pharmacokinetic profile of carbamazepine suspension. Epilepsia. May-Jun 1989;30(3):364-9. [Medline].

8. Goldfrank L, Flomenbaum NE, Lewin NA. Carbamazepine. In: Goldfrank's Toxicologic Emergencies. Appleton & Lange; 1994:594-5.

9. Graudins A, Peden G, Dowsett RP. Massive overdose with controlled-release carbamazepine resulting in delayed peak serum concentrations and life-threatening toxicity. Emerg Med (Fremantle). Mar 2002;14(1):89-94. [Medline].

10. Klimaszyk D, Lukasik-GLebocka M. [Cardiac toxicity of carbamazepine]. Przegl Lek. 2002;59(4-5):384-5. [Medline].

11. Litovitz TL, Clark LR, Soloway RA. 1993 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1994;12(5):546-84. [Medline].

12. Litovitz TL, Felberg L, Soloway RA, et al. 1994 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1995;13(5):551-97. [Medline].

13. Litovitz TL, Felberg L, White S, Klein-Schwartz W. 1995 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1996;14(5):487-537. [Medline].

14. Litovitz TL, Smilkstein M, Felberg L, et al. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1997;15(5):447-500. [Medline].

15. Micromedex. Toxicologic Managements of Carbamazepine. Healthcare Series Micromedex;95.

16. Miles MV, Lawless ST, Tennison MB, et al. Rapid loading of critically ill patients with carbamazepine suspension. Pediatrics. Aug 1990;86(2):263-6. [Medline].

17. Riva R, Contin M, Albani F, et al. Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: diurnal fluctuations and relationship with side effects. Ther Drug Monit. 1984;6(4):408-13. [Medline].

18. Romero Maldonado N, Sendra Tello J, Raboso Garcia-Baquero E, Harto Castano A. Anticonvulsant hypersensitivity syndrome with fatal outcome. Eur J Dermatol. Sep-Oct 2002;12(5):503-5. [Medline].

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20. Van Der Meyden CH, Kruger AJ, Muller FO, et al. Acute oral loading of carbamazepine-CR and phenytoin in a double-blind randomized study of patients at risk of seizures. Epilepsia. Jan-Feb 1994;35(1):189-94. [Medline].

21. Wada JA, Troupin AS, Friel P, et al. Pharmacokinetic comparison of tablet and suspension dosage forms of carbamazepine. Epilepsia. Jun 1978;19(3):251-5. [Medline].

Keywords

toxicity carbamazepine, carbamazepine toxicity, carbamazepine poisoning, 5H-dibenzazepine-5-carboxamide toxicity, antiepileptic drug toxicity, carbamazepine overdose, carbamazepine ingestion, carbamazepine exposure, antiepileptic drugs, AEDs, simple and complex partial seizures treatment, trigeminal neuralgia treatment, bipolar affective disorder treatment, iminostilbene derivative

Contributor Information and Disclosures

Author

Nidhi Kapoor, MD, Emergency Physician, Clinical Assistant Professor Emergency Medicine, Brown Medical School, Department of Emergency Medicine, Brown University School of Medicine
Nidhi Kapoor, MD is a member of the following medical societies: American College of Emergency Physicians, Rhode Island Medical Society, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Richard J Hamilton, MD, FAAEM, FACMT, Chairman, Department of Emergency Medicine, Drexel University College of Medicine
Richard J Hamilton, MD, FAAEM, FACMT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

David C Lee, MD, Research Director, Department of Emergency Medicine, Assistant Professor, North Shore University Hospital and New York University Medical School
David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD, ABAT is a member of the following medical societies: American Academy of Clinical Toxicology and American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Departments of Emergency Medicine (Toxicology), Environmental Medicine, Community & Preventive Medicine and Pediatrics, University of Rochester School of Medicine; Director, Finger Lakes Regional Resource Center; Managing and Associate Medical Director, Ruth A Lawrence Poison and Drug Information Center, University of Rochester Medical Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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