The significance of TDM of carbamazepine in clinical practice
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2024-11-27
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As a classic antiepileptic drug, carbamazepine has been widely used as a first-line drug since it was approved for marketing in 1974, which shows that the efficacy and safety of the drug have been clinically recognized. However, in view of the potential side effects and toxicity of the drug, TDM of carbamazepine has also accompanied the clinical application of the drug through decades of history. Even so, there is no clear guideline for the TDM of carbamazepine, and Dipesh Raj Panday's research team synthesized the available literature on carbamazepine TDM since 1966 to summarize the significance of carbamazepine concentrations.




Carbamazepine has significant interactions with several drugs

 
01
Drug interactions with other antiepileptic drugs


Treatment of patients with carbamazepine in combination with other antiepileptic drugs usually affects the blood levels of carbamazepine. For example, Vigabatrin may decrease the mean blood concentration of carbamazepine by enhancing the clearance of carbamazepine. Zonisamide has been reported to cause elevated carbamazepine concentrations in some patients.

 
02
Drug interactions with central nervous system drugs


Concomitant administration of carbamazepine with haloperidol (Haloperidol) can lead to an increase in serum concentrations of carbamazepine. Conversely, carbamazepine decreases haloperidol blood concentrations by 37%. Similarly, carbamazepine may cause a 71% decrease in the concentration/dose ratio (C/D) of olanzapine (Olanzapine). When taken concurrently with methadone (Methadone), carbamazepine may also cause a decrease in methadone concentrations and induce severe withdrawal symptoms.

  


03
Drug interactions with cardiovascular drugs


The combination of carbamazepine and amlodipine (Amlodipine) will reduce the metabolism of carbamazepine. Flunarizine  and nicardipine can also significantly increase the plasma concentration level of carbamazepine. Caffeine, on the other hand, is capable of attenuating the efficacy of carbamazepine.



The importance of TDM of carbamazepine

The blood concentration of carbamazepine has a direct correlation with the efficacy and side effects of the drug [1, 2]. However, considering that carbamazepine is affected by food, other drugs, etc. in many aspects such as absorption, metabolism, and clearance, the blood concentration is easy to go beyond the predetermined range. Especially in the process of combination drug administration, it is necessary to prevent the concentration from being too low or too high through TDM to ensure that the drug exerts normal therapeutic effects.

In addition, the relationship between blood concentrations of carbamazepine and the dose used is not linear, which makes it easy to under- or over-expose when regulating the amount of carbamazepine used, and therefore certain side effects such as reduced learning and memory capacity due to over-exposure occur frequently.TDM will help to control the probability of these types of events.

The metabolism of carbamazepine is also affected by genetic polymorphisms in individuals, so that inter-individual pharmacokinetic differences can be large in the absence of other factors interfering, and there is a certain degree of unpredictability in blood concentrations [3]. Studies have shown that the amount of patients with substandard drug concentrations remains high with routine carbamazepine administration, with 79.3% of patients having blood concentrations within the range of therapeutic levels (5-10 μg/ml), but 15.8% of patients at low levels and 4.9% at toxic levels. For this situation, TDM is the only means of monitoring and detecting abnormalities.


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The significance of TDM of carbamazepine in clinical practice


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The significance of TDM of carbamazepine in clinical practice


References:

1. Semah, F., et al., Carbamazepine and its epoxide: an open study of efficacy and side effects after carbamazepine dose increment in refractory partial epilepsy. Ther Drug Monit, 1994. 16(6): p. 537-40.

2. Krasniqi, S., et al., Carbamazepine and lamotrigine plasma concentrations in epileptic patients during optimising therapy. Med Arh, 2010. 64(2): p. 80-3.

3. Yeap, L.L., et al., Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis. Ther Drug Monit, 2014. 36(1): p. 3-9.




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