Clinically Significant Pharmacokinetic Drug Interactions with Carbamazepine

Spina, Edoardo; Pisani, F; Perucca, Emilio

doi:10.2165/00003088-199631030-00004

Cited by 298 publications

(176 citation statements)

References 162 publications

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“…As a consequence, VPA can reduce the metabolic elimination of the AEDs that are substrates for these enzymes, such as carbamazepine (CBZ), ethosuximide (ESM), lamotrigine LTG), and phenobarbital (PB) (2,4,5). In addition, VPA is highly bound to plasma albumin and hence has the potential to displace drugs from their plasma protein (6).…”

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confidence: 99%

Levetiracetam, a New Antiepileptic Agent: Lack of In Vitro and In Vivo Pharmacokinetic Interaction with Valproic Acid

2003

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Summary:Purpose: The novel antiepileptic drug (AED) levetiracetam (LEV; Keppra) has a wide therapeutic index and pharmacokinetic characteristics predicting limited druginteraction potential. It is indicated as an add-on treatment in patients with epilepsy, and thus coadministration with valproic acid (VPA) is likely. These studies were performed to determine whether coadministration of LEV with VPA might result in pharmacokinetic interactions.Methods: In vitro assays were performed to characterize the transformation of LEV into its main in vivo metabolite UCB L057. The reaction was examined for its sensitivity to clinically relevant concentrations of VPA. An open-label, one-way, onesequence crossover clinical trial was conducted in 16 healthy volunteers to assess further the possibility of any relevant pharmacokinetic interaction. Results:Human whole blood and, to a lesser extent, human liver homogenates were demonstrated to hydrolyze LEV to UCB L057, its main metabolite. The reaction possibly involves type-B esterases and is not affected by 1 mM VPA (i.e., 166 g/ml). Pharmacokinetic parameters of a single dose of LEV (1,500 mg) coadministered with steady-state concentrations of VPA (8 days of 500 mg, b.i.d.) did not differ significantly from the pharmacokinetics of LEV administered alone [area under the curve (AUC) of 397 and 400 g/h/ml, respectively]. Furthermore, LEV did not affect the steady-state pharmacokinetics of VPA.Conclusions: These findings suggest the absence of a pharmacokinetic interaction between VPA and LEV during shortterm administration, and suggest that dose adjustment is not required when these two drugs are given together.

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confidence: 99%

Levetiracetam, a New Antiepileptic Agent: Lack of In Vitro and In Vivo Pharmacokinetic Interaction with Valproic Acid

2003

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“…Despite the fact that its plasmatic level is lowered by drugs that induce hepatic metabolism 4 , it has relatively few adverse reactions and very little interaction with other medications 26 . When administered with carbamazepine, a potent enzymatic Cytochrome P450 inducer 27,28 , TPM undergoes 40% reduction of its plasmatic levels and clearance 28 . On the other hand, plasma levels of carbamazepine or its epoxide metabolite does not change significantly when TPM is added 29 .…”

Section: Discussionmentioning

confidence: 99%

Acute psychotic disorders induced by topiramate: report of two cases

Stella

Caetano

Cendes

et al. 2002

Arq. Neuro-Psiquiatr.

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-We report on two epileptic patients who developed acute psychosis after the use of topiramate (TPM). One patient exhibited severe psychomotor agitation, heteroaggressiveness, auditory and visual hallucinations as well as severe paranoid and mystic delusions. The other patient had psychomotor agitation, depersonalization, derealization, severe anxiety and deluded that he was losing his memory. Both patients had to be taken to the casualty room. After interruption of TPM in one patient and reduction of dose in the other, a full remission of the psychotic symptoms was obtained without the need of antipsychotic drugs. Clinicians should be aware of the possibility of development of acute psychotic symptoms in patients undergoing TPM treatment.KEY WORDS: psychiatric disorders, hallucination, delusion, topiramate. Episódio psicótico agudo induzido por topiramato: relato de dois casosRESUMO -Relatamos dois pacientes epilépticos que manifestaram quadro psicótico agudo induzido por topiramato (TPM). Um paciente apresentou agitação psicomotora grave, heteroagressividade, alucinações auditivas e visuais, e delírios de conteúdo paranóide e místico. O outro paciente apresentou agitação psicomotora, despersonalização, desrealização, ansiedade intensa e delírio de que estava perdendo a memória. Ambos os pacientes foram conduzidos ao serviço de emergência e, após a interrupção do TPM em um deles e redução da droga em outro, houve remissão total dos sintomas psicóticos sem necessidade de medicação antipsicótica. Alertamos os clínicos para o risco de surgimento de sintomas psicóticos em pacientes em uso do TPM.

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“…O controle do tempo de protrombina deve ser mais rigoroso inclusive na retirada da carbamazepina pelo risco de hemorragia fatal caso a dose de warfarin não seja ajustada (Spina, 1996).…”

Section: N T R O D U ç ã O / J U S T I F I C a T I V A : I N T R O unclassified

“…É substrato e inibidor de CYP 2C19, aumentando fortemente os níveis séricos de citalopram, podendo aumentar ainda os níveis de fenitoína e diazepam (Hardman, 1996;Johnson, 1999) a 50% do total de seu clearance (Spina, 1996). Para as drogas antiepilépticas, as interações farmacocinéticas são as mais presentes, mas as farmacodinâmicas também são relevantes (Patsalos, 2003).…”

Section: Furosemidaunclassified