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Anticonvulsants

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Valproate

can cause hyperammonemia even with normal lfts and low or therapeutic levels

lethargy, decreased mental status, ammonia >80

valproate blocks ammonia entrance into urea cycle

Must see 2 levels that are dropping by at least 20%. Send levels every hour in symptomatic overdose.

give charcoal even if >1 hr as valproate delays emptying

give 3 doses Q4 hours

    • Continuous venovenous hemodialysis (CVVHD): In cases of hemodynamic compromise, continuous renal-replacement therapy, eg, CVVHD may improve the elimination half-life and decrease the potential hemodynamic instability compared with standard dialysis.
  • Naloxone
    • Isolated case reports have described reversal of sedation with naloxone.
    • However, the administration of naloxone (including aggressive administration of 30 mg total) with no response has been reported.
  • L-carnitine
    • L-carnitine provides possible benefit, particularly in patients with concomitant hyperammonemia, encephalopathy, and/or hepatotoxicity. A relationship between VPA encephalopathy and hyperammonemia has been suggested. VPA combines with L-carnitine, which is an important component of long-chain fatty acid metabolism. In children with hyperammonemia who are taking VPA, L-carnitine reduces ammonia levels to the reference range.
    • One case report documented the administration of L-carnitine oral supplementation to a patient with acute VPA overdose. Levels of beta-oxidation metabolites (from mitochondrial metabolism, normal pathway) of VPA were low, levels of omega and omega-1 metabolites (nonmitochondrial-mediated metabolic byproduct) were elevated before treatment. After treatment, the former levels increased, and the latter decreased. Toxic metabolites (eg, 4-N-valproate, products of omega oxidation) initially detected in the urine were no longer present after carnitine supplementation.
    • The optimum route and dose of L-carnitine has not been determined. In a retrospective review of patients with hepatotoxicity secondary to VPA, improved outcomes were noted in patients who received IV L-carnitine compared with those receiving oral L-carnitine or control subjects who received only supportive care.
    • In a systematic review of 674 acute VPA overdoses, 55 doses of L-carnitine were given to 19 patients with isolated VPA ingestion and 196 doses were given to patients with mixed overdoses that included VPA. No patient developed hypotension or had an allergic reaction or other adverse effect.
    • One group recommends IV administration of L-carnitine, stating, “in any patient with coma, despite falling VPA concentrations, and climbing ammonia levels and (pending further study), in all patients with VPA concentrations greater than 450 mcg/mL (mg/L).” However, no dose for IV therapy was given.

 

L-Carnitine IV Dosing from Bellevue

100 mg/kg (max. 6 G) IVSS over 30 minutes

then 15 mg/kg Q 4 hours possibly for 72 hours

or until clin sx resolve and ammonia < 60, valproate < 100

comes in 1 gram vial, mix with normal saline

DOSING FOR HYPERAMMONEMIA

For symptomatic patients with hyperammonemia:

  • Loading dose of 100 mg/kg intravenously (6 g maximum) over 30 minutes followed by maintenance doses of 15 mg/kg every 4 hours over 10-30 minutes

For asymptomatic patients with hyperammonemia:

  • Oral doses of 100 mg/kg/day divided every 6 hours (3 g/day maximum).

 

Maryland ToxTidbits

Valproic acid is the active ingredient in the prescription medications Depakote, Depakote ER, Depakene, and

Depacon. These medications are used for the treatment of seizure disorders, prevention of migraine headaches,

and treatment of manic episodes related to bipolar disorder. The exact mechanism by which valproic

acid exerts its therapeutic effect is not known. The most prominent theory is that valproic acid increases the

concentration of gama-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain.

Hepatotoxicity and liver failure resulting in death have occurred in patients receiving therapeutic doses of valproic

acid, usually within the first six months of starting therapy. Patients with an increased risk of liver toxicity

from valproic acid include children, patients with congenital metabolic disorders, and those on multiple antiseizure

drugs. Patients should be closely monitored for weakness, lethargy, vomiting, facial swelling, and anorexia

while taking this medication.

Acute valproic acid overdoses may cause vomiting, confusion, and tachycardia. Coma, hypotension, respiratory

depression, metabolic acidosis, hyperammonemia, renal failure, QTc prolongation and cardiopulmonary

arrest can occur in severe overdoses and can be seen up to 18 hours following ingestion. Serum valproic acid

levels may be obtained but these levels are usually not reliable at predicting clinical effects. A level of 50-100

mcg/ml is considered therapeutic, and levels above 850 mcg/ml are generally seen in patients with more serious

effects such as coma and respiratory depression. Enteric coated valproic acid (Depakote, Depakote ER)

absorption may be delayed with peak levels occurring 6-8 hours following ingestion; therefore, repeat valproic

acid levels should be obtained to ensure that levels are not continuing to rise.

In patients who have ingested an overdose of valproic acid, treatment includes a dose activated charcoal to

prevent absorption, a second dose of activated charcoal if a sustained release formulation is ingested or if

levels continue to rise, L-carnitine for hyperammonemia or hepatotoxicity, and possibly hemodialysis or hemoperfusion

in patients with severe intoxication not responding to supportive therapy.

 

 

Overdoses with anticonvulsants are frequently reported. In 2004, a total of 40,021

exposures to anticonvulsants were reported to the American Association of Poison Control

Centers. A little more than half of these exposures were to “new” anticonvulsants:

gabapentin, lamotrigine, topiramate, leveritacetam, tiagabine, oxcarbazepine, vigabatrin,

zonisamide and pregabalin. We will review the toxicity of these new agents and discuss

management of overdoses.

Gabapentin (Neurontin®)

Gabapentin is a cyclohexane derivative of GABA, approved as adjunctive therapy for the

management of partial seizures in adults and children and post-herpetic neuralgia. In a

case series of 20 gabapentin overdoses, lethargy, ataxia and gastrointestinal symptoms

developed within 5 hours and resolved over 4-24 hours. In one case report of a chronic

overdose in a patient with renal failure, tremulousness and cognitive deficits were noted.

The symptoms resolved following a dose adjustment. Catatonia following abrupt withdrawal

of gabapentin is described. The treatment of patients with gabapentin overdose starts with

administration of activated charcoal to limit absoprtion. There is no specific antidote.

Patients with persistent neurologic symptoms need to be admitted to the hospital. Hemodialysis

and hemoperfusion are not generally required, except in severely symptomatic

patients with significant renal impairment.

Lamotrigine (Lamictal®)

Lamotrigine is approved as an adjunctive medication for the treatment of partial seizures in

adults and pediatric patients. It is also approved for maintenance treatment of bipolar mood

disorder. Lamotrigine binds to sodium channels and prolongs their recovery from

inactivation. At therapeutic concentrations, the sodium channel blockade is selective. At

toxic levels, the selectivity is lost and all sodium channels are inhibited, and some GABA

enhancement is detected.

Neurologic manifestations such as lethargy, ataxia, nystagmus and gastrointestinal

symptoms are described following lamotrigine overdose. A previously healthy toddler

developed two seizures after an acute unintentional lamotrigine overdose. The lamotrigine

level two hours post-ingestion was 3.8 mg/L. Repeat levels were lower. Seizure activity did

Overdoses Of Newer Anticonvulsants

S

UZANNE DOYON, MD, ACMT

M

EDICAL DIRECTOR

M

ARYLAND POISON CENTER

March 2006

Volume 22 Issue 1

New

anticonvulsants

are responsible

for over 50% of

anticonvulsant

overdoses

reported to

poison centers.

All of these

drugs produce

some degree of

CNS impairment

with notable

differences in

other toxic

effects.

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Overdoses Of Newer Anticonvulsants

not recur and the ataxia and muscle weakness resolved over 48 hours. Coma and cardiac conduction disturbances

may also occur following large overdoses of lamotrigine. Therefore, lamotrigine behaves much like other sodium

channels blockers, such as cyclic antidepressants, in overdose situations.

Chronic overdoses of lamotrigine result in multiorgan involvement, including rashes, elevation in hepatic

aminotransferases, rhabdomyolysis and elevation of serum creatinine phosphokinase.

The treatment of lamotrigine

overdose starts with the administration of activated charcoal to limit absorption. Observation and ECG monitoring are

recommended. Prolongation of the QRS interval beyond 100 msec requires admission to telemetry and

administration of sodium bicarbonate 1-2 mEq/kg intravenously, until serum pH is 7.45-7.55. Lamotrigine-induced

seizures should be treated with benzodiazepines. There are no data on the value of hemodialysis and hemoperfusion.

Topiramate (Topamax®)

Topiramate is a sulfamate-substituted monosaccharide approved as adjunctive therapy for adults with partial-onset

seizures. It is also used for migraine prophylaxis and for the treatment of infantile spasms and other refractory

epilepsies in infants and children. Topiramate binds to the

kainate glutamate receptor subtype and blocks the Na+

entry into the neuronal cell.

Lethargy, ataxia, nystagmus, myoclonus, coma, seizures and status epilepticus are reported following topiramate

overdose. Interestingly, repetition of words (echolalia) and repetitive movements of the mouth (oral-buccal dyskinesia)

are reported. Non anion gap metabolic acidosis due to inhibition of renal cortical carbonic anhydrase may be

present, along with hyperchloremia and hypokalemia (2.0-3.2 mEq/L). The metabolic acidosis appears within hours

of ingestion and can persist for days.

Activated charcoal is recommended. Monitoring of electrolytes and blood gases is important. Severe hyperchloremic

metabolic acidosis should be treated with sodium bicarbonate 1-2 mEq/kg intravenously. Systemic administration of

sodium bicarbonate may impair the anticonvulsive effect of topiramate, however. Therefore, admission to a higher

level of care is recommended in the context of sodium bicarbonate administration. Hemodialysis is recommended in

severe overdoses associated with neurologic impairment, electrolyte abnormalities that have failed to respond to

conventional therapy and/ or renal insufficiency. Hemodialysis is especially useful to correct intractable metabolic

acidosis.

Tiagabine (Gabatril®)

Tiagabine inhibits the reuptake of GABA and is approved as an adjunctive treatment for focal and secondarily generalized

seizures. It is also being prescribed for a variety of psychiatric disorders. Tiagabine inhibits the GAT-1 GABA

transporter and prevents the re-uptake of GABA into presynaptic neurons.

Lethargy, tachycardia, facial myoclonus (grimacing), nystagmus and posturing are described in overdoses. The

Maryland Poison Center has been contacted about many unusual manifestations of tiagabine poisoning, including

bizarre facial grimacing and bizarre myoclonic jerks. At very high plasma levels, seizures and status epilepticus are

reported. A previously healthy toddler developed three seizures after an unintentional overdose of tiagabine. Serum

level of tiagabine was 530 ng/mL. An adult patient presented in status epilepticus and was misdiagnosed until a very

high tiagabine level was reported and an acute overdose was confirmed. Most symptoms last 12-24 hours and result

in no permanent neurologic sequelae.

Activated charcoal and supportive care are recommended for the management of tiagabine overdose. Seizures

respond to administration of benzodiazepines and refractory status epilepticus should be treated with barbiturates.

For poisoning or overdose questions and consultations,

call the Maryland Poison Center at

800-222-1222

Levetiracetam (Keppra®)

 

Levetiracetam is approved as an adjunct medication for the management of intractable epilepsy. Its mechanism

of action is poorly understood, although it inhibits pre-synaptic N-type calcium channels. Recent research has

illustrated that levetiracetam has both a neuroprotective and an anti-inflammatory effect. In one case report of

levetiracetam overdose, lethargy, coma and respiratory depression were reported. Nystagmus was absent.

Symptoms persisted for 24 hours. The management of levetiracetam overdoses starts with the administration of

activated charcoal to limit absorption. Monitoring for CNS depression and supportive care are recommended.

Oxcarbazepine (Trileptal®)

Oxcarbazepine is a keto-analog of carbamazepine which functions as a prodrug. It is rapidly converted to the

pharmacologically active 10-monohydroxy-10-oxocarbazepine metabolite. Its mechanism of action is similar to

carbamazepine (Tegretol®), except it is a less potent inducer of CYP3A4. Oxcarbazepine overdoses present

with nystagmus, ataxia, and dysarthria, much like carbamazepine overdoses. Oxcarbazepine will be detected by

the carbamazepine assay and levels will be in the order of 1-3 mg/L. Treatment of oxcarbazepine overdoses

closely ressembles that of carbamazepine and starts with the administration of activated charcoal. Occasionally,

and especially when faced with very large overdoses, multiple doses of activated charcoal are recommended.

Zonisamide (Zonegran®)

Zonisamide

inhibits the flow of calcium through low voltage T-type calcium channels, thus reducing the

“pacemaker” current

. It also inhibits sodium channels and possibly carbonic anhydrase. Somnolence is a

commonly reported adverse effect. Although experience with overdoses of zonisamide is limited, one paper

reported status epilepticus, coma and death following an acute zonisamide overdose. Management of

zonisamide overdose includes administration of activated charcoal and monitoring for CNS effects.

Pregabalin (Lyrica

®)

Pregabalin is a new gabapentinoid. Chemically related to gabapentin, it is more potent, achieving efficacy at

lower doses. Like gabapentin, pregabalin modulates gabaminergic neurotransmission and calcium channel

activity. It is approved as an adjunct for the treatment of partial seizures and for the management of diabetic

neuropathic pain and post-herpetic neuralgia. Overdoses of pregabalin have not been reported. Thus far, however,

limited unpublished experience with pregabalin shows that it is fairly well-tolerated in acute overdoses. The

management of pregabalin overdoses includes administration of activated charcoal and monitoring for CNS

depression.

In conclusion

,

new anticonvulsants are now responsible for over 50% of anticonvuslant overdoses. All

overdoses to new anticonvulsant agents will present with some degree of CNS impairment but there are quite a

few notable differences. Although serum electrolytes are important to obtain in all instances, they are especially

important in topiramate and zonisamide overdoses because of their capacity to inhibit carbonic anhydrase

activity. Specific serum levels of anticonvulsants are not usually recommended in the acute setting, except when

the patient develops seizures or status epilepticus.

Treatment of these overdoses begins with administration of single-dose activated charcoal. Correction of

electrolyte abnormalities is recommended, especially in cases of topiramate and zonisamide overdoses. There

are no effective antidotes. Anticonvulsant-induced seizures usually respond to benzodiazepines and barbiturates.

QRS prolongation should be treated with sodium bicarbonate. Hemodialysis can be considered in cases of lifethreatening

overdoses of gabapentin and topiramate, but is not generally required; supportive care is sufficient in

most instances. It is unclear whether hemodialysis affects the outcome of pregabalin or zonisamide overdoses.

References for this article are available on request.

 

(JEM 2010;38(2):231)

 

 

Seziure Med toxicity obtain levels out to at least twelve hours     carbamazepine is similar to TCAs so may cause card abn, though unlikely multi-dose charcoal is mainstay accumulation of an active metabolite can cause continued sx even as serum levels drop   gabapentin undergoes only renal excretion can be dialyzed   tiagabine 3 times daily dose can cause seizure   lamictal nystagmus and giggling seizure and coma in a small subset

 

 

 

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Carbamazepine

Risk assessment Carbamazepine is an anticonvulsant agent that is also increasinglyprescribed as a mood stabiliser. The clinical features of toxicityafter acute overdose are dose related and correlate well withserum levels. They are predominantly neurological and usuallyof delayed onset because of delayed and erratic absorption ofthe drug. Ingestions of >20 mg/kg result in levels abovethe normal therapeutic range (6–12 mg/l, 17–51 mmol/l) and are associated with neurological signs and symptoms includingataxia, nystagmus, mydriasis, movement disorders and the anticholinergictoxidrome. More severe neurotoxicity in the form of severe centralnervous system (CNS) depression is expected to develop afteringestion of doses >50 mg/kg. Minor changes on electrocardiographyare common after large ingestions, but major cardiotoxicityis rare.1,2

This patient had taken a massive overdose of 20 g or 400 mg/kgof carbamazepine. We expect her to develop neurological symptomsprogressing to coma requiring intubation and ventilation inthe next 8 h. She may even develop more unusual complicationsassociated with massive overdose, including seizures and cardiovascularinstability.

Armed with this individualised risk assessment, we can now plana rational management plan for our patient.

 

Serial serum carbamazepine levels, ideally performed every 4 h until they peak, are useful to refine risk assessment, and monitor clinical course and response to enhanced elimination techniques. Levels >12 mg/l (50 mmol/l) are associated with ataxia and nystagmus, and levels >40 mg/l (170 mmol/l) are associated with coma, respiratory depression and seizures.1,3 Peak levels may be delayed up to 96 h after massive ingestion of controlled-release preparations.4

The prolonged absorption of carbamazepine means that administration of oral activated charcoal is likely to reduce drug absorption even when given many hours after the overdose. This potential to reduce the duration and severity of toxicity must be balanced against the risk of subsequent aspiration of charcoal associated with CNS depression. If CNS depression over the next few hours is anticipated, then it is safer to withhold treatment with activated charcoal until after the airway is secured with endotracheal intubation.1,5 Whole-bowel irrigation has been advocated as a method of decontamination after carbamazepine overdose, particularly of controlled-release preparations. However, as this procedure usually takes about 6 h to complete, it can be safely carried out only if the airway is first secured. Whole-bowel irrigation is technically more difficult in the intubated and ventilated patient, and is further complicated if ileus develops as a result of the anticholinergic effects of carbamazepine. In our patient, given the massive nature of the overdose, administration of activated charcoal is indicated, but only after the airway is first secured as development of considerable CNS depression over the next few hours is anticipated. Whole-bowel irrigation has a considerable risk of complications, without defined additional benefit. Enhanced elimination Administration of multidose activated charcoal enhances elimination of carbamazepine by interruption of enterohepatic circulation.5 This intervention has the potential to reduce the duration of toxicity. A potential major adverse effect is acute bowel obstruction from charcoal concretions, especially if anticholinergic ileus develops. Haemoperfusion or haemodialysis also improves elimination of carbamazepine.6 This invasive, resource-intensive intervention is not justified unless risk assessment indicates potential for prolonged coma, seizures, cardiovascular instability or other adverse outcome not easily managed with supportive care. In this patient in whom coma is anticipated, initiation of multidose activated charcoal is justified once the airway is secured. It should be continued until ileus develops or coma resolves. Urgent implementation of haemodialysis is not indicated but might be useful at a later time depending on clinical progress and serial serum carbamazepine levels.

 

Carbamazepine overdose

 

  • Absorption is delayed and erratic
  • Dose>20 mg/kg: anticipate mild–moderate central nervoussystem and anticholinergic effects
  • Dose >50 mg/kg: anticipatefluctuation in mental status with intermittent agitation followedby coma requiring intubation and ventilation within 12 h
  • Cardiovascularinstability may occur with very high doses
  • Enhanced eliminationwith repeat-dose activated charcoal, haemodialysis or haemoperfusionis clinically useful in selected cases

 

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Phenytoin (Dilantin®)

Phenytoin (Dilantin®)

Phenytoin is still one of the most widely used antiepileptics despite its unattractive side effect profile and relatively narrow therapeutic-to-toxic ratio (7).  Phenytoin is available orally and intravenously; a newer form, fosphenytoin, which is converted to phenytoin after administration, is designed for intravenous or intramuscular use.  In addition to central sodium channel blocking activity, phenytoin is also a Vaughn-Williams class IB antidysrhythmic, though it is rarely used for this purpose.  The most feared toxicity of phenytoin is cardiotoxicity; however, this effect is due not to the phenytoin but instead to the diluent used for its IV form, propylene glycol.  Because of the propylene glycol diluent, too-rapid infusions of phenytoin may cause hypotension or dysrhythmias, a problem that rarely occurs if infusion rates are watched closely.  Phenytoin is irritating to the tissues if it extravasates, and may cause tissue sloughing.  Fosphenytoin does not have these effects and is generally regarded as being safer to administer parenterally than phenytoin, though it is significantly more expensive.  There have been case reports of fosphenytoin causing hemodynamically significant bradycardia (8).

 

Typical therapeutic phenytoin serum levels are 10-20 μg/ml, though some patients will be therapeutic at both lower and higher levels.  Acute toxicity is generally seen at levels > 20 mg/dL.  The effects from acute excess phenytoin ingestion are generally neurologic-ataxia, nystagmus, and in more serious cases CNS depression.  Dysrhythmias from oral phenytoin overdose have not been described.  Nystagmus is the earliest reliable sign of toxicity.  This is seen in both acute ingestion and subacute toxicity.  While intentional overdoses of oral phenytoin are not uncommon, iatrogenic overdoses occur frequently.  In general, this is a result of: 1) healthcare providers not taking the time to accurately calculate a loading dose of phenytoin based on weight and available serum levels, and 2) not correctly interpreting a serum level in terms of time since last dose and serum albumin level.  While severe morbidity or mortality from phenytoin overdose is rare, it nonetheless frequently entails a hospitalization and increased health care expenditure (7).

 

Table 2: Correlation of Serum Phenytoin Levels to Clinical Presentation (1)

Level > 20 μg/ml= nystagmus

Level > 30 μg/ml= ataxia

Level > 50 μg/ml= coma

Level > 100 μg/ml= potentially lethal

 

 

Chronic effects from phenytoin include gingival hyperplasia, anemia and hepatotoxicity.  Phenytoin is implicated in multiple drug interactions (see table 3).  While it a good anticonvulsant for several types of seizures, it is not particularly effective in toxin-induced seizures, which are generally due to generalized CNS excitation and not due to a single epileptogenic focus.  In a patient with suspected overdose and a history of epilepsy who is seizing, phenytoin loading should be undertaken if the level is subtherapeutic, understanding that other agents, such as benzodiazepines, should be contemporaneously administered.  The other common complication many physicians are aware of is tissue necrosis if the IV infusion extravasates.  This has been referred to as “purple glove syndrome” and has been reported to be more significant when 5% dextrose is used as the infusion fluid instead of normal saline (1).

Purple Glove Syndrome

 

 

Table 3: Antiepileptic Drug Interactions

Levels of these drugs are INCREASED by phenytoin

Levels of these drugs are DECREASED by phenytoin

These Drugs INCREASE phenytoin levels

These drugs DECREASE phenytoin levels

Acetaminophen

Phenobarbital

Primidone

Amiodarone

Carbamazepine

Oral contraceptives

Valproic Acid

Cyclosporine

Methadone

Theophylline

Quinidine

 

Amiodarone

Cimetidine

Ethosuximide

Fluconazole

INH

Oral Contraceptives

Valproic Acid

TMP-SMX

Diazepam

Ethanol

Phenobarbital

Rifampin

Sucralfate

Theophylline

 

 

There are several caveats to phenytoin dosing. (8, 9) The metabolism of the drug is saturable, meaning that as dose of the drug increases, its half life is prolonged and once the metabolic pathway is saturated, small increases in drug dose lead to large increases in plasma levels.  Phenytoin, similar to salicylates, crosses over from first order kinetics (a certain percentage of drug is removed per unit time) to zero order kinetics (fixed amount of drug removed per unit time) at higher levels.  Thus, at higher levels, metabolism of the drug is slower.  This is important given the frequency of phenytoin loading in the ED; if the Emergency Physician overshoots with the loading dose, the phenytoin level can easily go into the toxic range.  Phenytoin is bound to albumin, and as albumin levels fall, the amount of free drug increases.  When preparing to administer phenytoin, it is preferable to correct for the plasma albumin level to accurately calculate the needed dose.  This is often not routinely done and in many patients will not result in significant change in the dosing of phenytoin. Those patients more likely to be hypoalbuminemic, such as malnourished patients, alcoholics, or those with liver disease, should have correction for serum albumin (see table 4). Furthermore, the oral absorption of phenytoin is slow; if a level is drawn soon after an oral dose, then it will appear low and if loading is done based on this falsely low level, the patient may be pushed into the toxic range (3).

 

Table 4: Correction of phenytoin levels in hypoalbuminemia

Corrected level = phenytoin level/[(albumin x 0.2) + 0.1]

Example: phenytoin level = 10, albumin = 2.2; 10/ (2.2 x 0.2 ) + 0.1= 10/0.54=  18.5

 

 

Management of phenytoin toxicity is straightforward.  If a patient develops cardiotoxic effects from an IV infusion, slow the infusion rate and administer IV fluids and other appropriate supportive care.  If an oral overdose is suspected, then a dose of activated charcoal is appropriate providing the patient has a patent airway and the time of ingestion is recent (generally recommended within one hour).  Data are conflicting on the benefit of multi-dose activated charcoal for this ingestion; generally, phenytoin is not included on the list of drugs for which multi-dose activated charcoal is indicated.  Widening of the QRS complex and QT intervals may be seen from intravenous administration of phenytoin and is generally self-limiting.  Stopping the phenytoin and monitoring serial drug levels and neurologic exams is in most cases all that is required.  As the neurotoxicity resolves and the patient reaches a therapeutic level again, then phenytoin can be restarted.  For patients chronically on phenytoin, the level should not be allowed to fall to zero as this places the patient at risk for seizures. There are limited data with extended-release forms of phenytoin in overdose, though it is advisable to check serial levels to avoid missed toxicity.

 

Not all patients with signs of phenytoin toxicity require admission.  Those with levels in lower ranges of toxicity, no significant comorbidities, with someone reliable to watch them, and good follow-up for reassessment and repeat drug levels within 24 hours may be discharged.  Patients who are significantly ataxic, with altered mentation, or with any question about safety of their outpatient environment or ability to follow-up should be admitted for observation.

(EMEDHOME)

corrected phenytoin = phenytoin ((albumin x 0.2) + 0.1) level >20=nystagmus >50=coma >100=potentially lethal

Neurology. 1985 Dec;35(12):1769-72. Links Incidence of seizures with phenytoin toxicity. Among 50 patients with phenytoin intoxication, 14 had seizures during the episode. Seizures in 9 of these 14 patients probably resulted from poor seizure control despite high phenytoin levels, but in 5 cases, attacks were attributed to phenytoin toxicity. The only factor that seemed to correlate with seizures was a serum phenytoin level over 30 micrograms/ml. No demographic, metabolic, neuropsychiatric, or therapeutic variables were predictive; nor were any other symptoms of toxicity particularly likely to be found in association with seizures. Seizures are an occasional manifestation of phenytoin toxicity, particularly when levels are high.

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Anticonvulsant hypersensitivity syndrome

dilantin phenobabrb carbamazepine lamictal use valproate instead

 

 

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