Delayed Elevation in Carbamazepine Concentrations After Overdose

Abstract

An initial carbamazepine concentration may initially be supratherapeutic, therapeutic, or even subtherapeutic only to persist to rise over time. The aim of this study was to report the frequency of toxic carbamazepine concentrations continuing to rise and to estimate how often an initially therapeutic or subtherapeutic concentration misrepresents the potential toxicity of an acute carbamazepine overdose. An 8-year retrospective search of all carbamazepine exposures reported to the Illinois Poison Center (January 1, 2001 through December 31, 2008) was reviewed. Inclusion criteria were acute poisonings with a documented carbamazepine concentration of >12 μg/mL at any time. Those with initial concentrations of >12 μg/mL that subsequently increased over time were recorded. Additionally, those cases that initially had therapeutic (4-12 μg/mL) or subtherapeutic (<4 μg/mL) concentration were identified. Descriptive statistics were used to analyze the data. A total of 1424 cases were reported. Of the 523 patients with documented concentrations of >12 μg/mL, 93 patients (17.8%) had initial carbamazepine concentrations >12 μg/mL and continued to rise. Sixteen patients (3.5%) had initial carbamazepine concentrations that were therapeutic (4-12 μg/mL) and 7 patients (1.3%) had initial carbamazepine concentrations <4 μg/mL before rising >12 μg/mL. Certain patients had progressive decreases in level of consciousness corresponding to increasing carbamazepine concentrations. Additionally, several patients with initial levels of therapeutic or subtherapeutic concentration later became comatose and required ventilator management. Initial serum carbamazepine concentrations can be misleading. Serial measurements documenting a declining carbamazepine concentration or prolonged observation are recommended when managing these overdoses.

Successful treatment of a case with concurrent ingestion of carbamazepine overdose and grapefruit juice

“…Although the peak blood CBZ concentration typically appears 6–24 h after ingesting a normal therapeutic dose, a massive overdose may delay the peak concentration until more than 72 h after ingestion . In cases of CBZ overdose, blood CBZ concentrations have also been known to continue rising after the initial measurement . Although there was a concern that the extended increase in CBZ concentration was caused by grapefruit juice, the CBZ concentration had decreased by the second measurement (at 12 h, Fig.…”

LC–MS3 Strategy for Quantification of Carbamazepine in Human Plasma and Its Application in Therapeutic Drug Monitoring

“…It is necessary to adjust dosages to achieve the best therapeutic effect while avoiding low (subtherapeutic) and high (toxic) levels. The optimal plasma level of carbamazepine for the treatment of epilepsy is reported to be 4-12 µg/mL [11][12][13][14].…”

Multiple drugs poisoning resulting in ARDS

“…Geçici olarak yaralanma veya solunum sıkıntı-sına yol açabilen bu durumlar, uzun sürdüklerinde yoğun bakım ihtiyacı da doğurabilmektedir. Karbamazepin gibi sık kullanılan bir antiepileptik ve antipsikotik ilaç zehirlenmesinde dahi, serumda ölçü-lebilen ilaç düzeyinin geç yükselmesi [4] nedeniyle tanıda zorluklar yaşanabilir, hemodiyaliz gibi erken dönemde etkili olabilecek tedaviler [5] dahi, gecikmeler nedeniyle etkisiz kalabilir.…”