Download Carbamazepine overdose after exposure to simethicone

Carbamazepine overdose after exposure to simethicone : a case report
Ozlem GUNEYSEL, MD; Ozge ONUR, MD; Arzu DENIZBASI, Assoc Prof.
Marmara University, School of Medicine Department of Emergency Medicine
Corresponding author:
Dr Ozlem GUNEYSEL
Marmara Universitesi Hastanesi Acil Servis
Tophanelioglu C Yurtacan S No 13-15
Altunizade –USKUDAR/ISTANBUL
TURKEY
e-mail
: [email protected]
Fax
: +90216 326 95 78
Phone
: +90532 221 13 68
E-mail adresses:
OG: [email protected]
OO: [email protected]
AD: [email protected]
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Abstract
Introduction Carbamazepine is an anticonvulsant drug and is also used as a
treatment for patients with manic-depressive illness, post herpetic neuralgia, or
phantom limb pain. The drug itself has many drug interactions. Simethicone is an
antifoaming agent and known as an inert material. There is no known drug interaction
with carbamazepine.
Case presentation A 45 year old male patient with a medical history of
epilepsy presented to our emergency room with complaints of vertigo, gait
disturbance, dizziness, slurred speech, and diplopia. He was using Carbamazepine
400 mg three times /day for four years and Keppra twice daily for one year. No other
drugs were reported except a history of two days Simethicone usage.
Carbamazepine serum level was 34.2 µg/ml (4-11 µg/ml). Patient was taken to the
neurology inpatient unit with a diagnosis of carbamazepine intoxication.
Carbamazepine was withdrawn. Intravenous hydration and cardiac monitorization
were done. After 36 hours his serum carbamazepine level was normalized and
neurological exam was intact.
Conclusion The mechanism is unknown but a risk of overdose must be taken
under consideration during prescribing simethicone to a patient who is using
carbamazepine.
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Background
Carbamazepine is an anticonvulsant drug, received approval for use as an
antiepileptic agent in the United States in 1974. It is also used as a treatment for
patients with manic-depressive illness, post herpetic neuralgia, or phantom limb pain.
Therapeutic plasma concentration is 4- 12 mg/L. It is approximately 75-80% protein
bound. Carbamazepine is oxidized by hepatic microsomal enzymes to produce its
active metabolite, carbamazepine 10, 11- epixode. In terms of drug interactions,
carbamazepine induces the metabolism of other anticonvulsant drugs. Inhibitors of
hepatic microsomal enzymes such as erythromycin, clarithromycin, and cimetidine
increase carbamazepine levels [1].
Simethicone is an antifoaming agent that acts by altering the surface tension
of mucus-entrapped gas bubbles in the digestive tract, allowing them to coalesce and
disperse [2]. It is excreted unchanged in the feces; it is not absorbed [3]. There is no
known drug interaction with carbamazepine.
We present a case of carbamazepine overdose after exposure to simethicone.
After cessation of simethicone therapy normal drug levels of carbamazepine were
obtained again with standard dose of the drug.
Case presentation
A 45 year old male patient with a medical history of epilepsy presented to our
emergency room with complaints of vertigo, gait disturbance, dizziness, slurred
speech, and diplopia. He was using Carbamazepine (Karazepin®) 400 mg three
times /day for four years and Keppra® twice daily for one year. No other toxin,
alcohol, herbal products, drugs were reported except a history of two days
Simethicone (Metsil®) usage. He had a blood pressure (BP) of 115/70 mmHg, pulse
rate (PR) of 88 beats/min, respiratory rate (RR) of 18 breaths /min. The patient had a
normal mental status and was able to give a reliable history. He denied trauma, extra
drug dosage or suicidal attempt. In his neurological examination, pathological
findings were bilateral nystagmus, dysarthria, diplopia, ataxic walking. He had a
serum carbamazepine level reported as 10.5 µg/ml (reference range: 4-11) two days
before, confirmed in neurology outpatient clinic.
The initial laboratory findings were as follows: Hematocrit,41.5, prothrombin
time, 12.3 sec (reference range,11-13), INR, 1.02 , creatinine, 0.97 mg/dl (0.5-1.10
mg /dl); glucose, 102 mg/dl (70-110mg/dl); serum alanine aminotransferase (ALT), 16
U/L (10–37 U/L); aspartate aminotransferase (AST), 17 U/L (10–40 U/L); alkaline
phosphatase (ALP), 238 U/L (0–270 U/L); γ-glutamyltransferase (GGT), 46 U/L (7–49
U/L); total bilirubin, 0.54 mg/dL (0.2–1.0 mg/dL); carbamazepine serum level, 34.2
µg/ml (4-11 µg/ml).
Cranial computed tomography (CT) scan was normal.
Patient was taken to the neurology inpatient unit with a diagnosis of
carbamazepine intoxication. Carbamazepine was withdrawn. Intravenous hydration
and cardiac monitorization were done. After 36 hours his serum carbamazepine level
was normalized (level at 24 hours: 17.6, level at 36 hours: 11.4) and neurological
exam was intact. In control visit he was warned about simethicone. There is no
problem since 6 months.
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Discussion
Carbamazepine (CBZ) is one of the most commonly prescribed drugs for the
prevention of partial seizures as well as for treatment of generalized tonic-clonic
seizures and trigeminal neuralgia [4]. The most important interactions affecting the
disposition of CBZ are those resulting in the induction of its metabolism. Clinically, a
variety of drug interactions between CBZ and co-administered drugs have been
reported. The actions of most drugs that affect CYP3A4 by inhibition or induction
manifest as drug interactions with CBZ [5,6]. However, there has been no
demonstration of simethicone and carbamazepine interaction until now.
Simethicone has been used as an adjunct in the treatment of various clinical
conditions in which gas retention may be a problem including dyspepsia, infant colic,
peptic ulcer, irritable colon. It also appears to be helpful as an adjunct to various
procedures such as colonoscopy and bowel radiography [7]. It is a mixture of liquid
dimethylpolysiloxanes which have antifoaming activity. It acts in the stomach and
intestines by altering surface tension of gas and mucus bubbles enabling them to
coalesce. It is reported as physiologically inert, no toxic effects are reported in
ingestion [8].
Because of its availability, CBZ is a drug commonly involved in accidental and
intentional overdoses. The American Association of Poison Control Centers reported
a total number of 18.201 CBZ overdoses from 1999 to 2001. This led to 18 deaths
[9]. Acute CBZ toxicity presents with cardiac, respiratory, and neurological effects.
Neurological signs include loss of consciousness, seizures, ataxia, choreoathetosis,
myoclonus, motor restlessness, mydriasis, and nystagmus [10]. Most of these signs
were positive in our patient.
In this case we present a CBZ toxicity due to simultaneous intake of
simethicone. Both drugs are widely used, but there has been no studies searching
effect of simethicone on the pharmacokinetics of CBZ up to date. Due to simethicone
is an inert material, we could not explain the mechanism of action. But there was no
other factor for such a patient receiving CBZ for four years, no adverse events were
reported by him until the use of simethicone. This patient’s directory follow-up was
excellent.
Conclusion
A risk of overdose must be taken under consideration during prescribing
simethicone to a patient who is using CBZ.
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Competing interests
The authors declare they have no competing interests.
Authors’ contributions
OG identified the relevant case, conducted the literature search and wrote the
discussion
OO wrote the case presentation
AD involved in conception of the article and revising it critically for important
intellectual data before final approval
All authors read and approved the final manuscript
Consent : Written informed consent was obtained from the patient for publication of
this case report.
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