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
]. CBZ interacts with a number of drugs other than anticonvulsants and there are a number of mechanisms involved. The absorption of oral CBZ is slow, erratic and unpredictable. Peak plasma concentrations generally occur 4 to 8 hours after ingestion, but may require up to 26 hours to peak. It is rapidly distributed into the body and has about 75% to 78% protein binding. CBZ is metabolized in the liver by the cytochrome P450 system and undergoes almost complete biotransformation to several metabolites. The most important interactions affecting the characteristics 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
]. However, there has been no demonstration of simethicone and CBZ 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 and 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 the surface tension of gas and mucus bubbles, enabling them to coalesce. It is reported as physiologically inert, and no toxic effects are reported on ingestion [8
As it is widely available, 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, leading 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.
We have presented a case of CBZ toxicity due to simultaneous intake of simethicone. The Naranjo adverse drug reaction probability scale was used as an objective measure of causality; a score of 7 was found [11
]. Based on a score of 7 on the Naranjo adverse drug reaction probability scale, simethicone was the probable cause of CBZ toxicity in this patient. Both drugs are in wide use, but to date there have been no studies examining the effects of simethicone on the pharmacokinetics of CBZ. As simethicone is an inert material, we could not explain the mechanism of action. This interaction may be caused by extrahepatic enzymatic processes. There are some reports regarding absorption processes and CBZ therapeutic levels. It was confirmed that simultaneous oral administration of TJ-9 (Sho-saiko-to extract powder) with CBZ to rats decreased gastrointestinal absorption of CBZ, without affecting the metabolism of CBZ [12
]. In another study it was shown that concomitant administration of Coca-Cola (an acidic beverage) enhanced the rate and extent of absorption of CBZ [13
]. An absorption effect may therefore be responsible for CBZ toxicity in a patient taking simethicone and CBZ together.
In a patient with CBZ toxicity, possible causes such as multiple drug ingestions, beverages, herbal products, drug overdoses and liver function abnormalities should be considered. Our patient had been taking CBZ for 4 years; during this period no adverse events were reported until simethicone usage. This patient's follow-up was excellent.