Active Pharmacovigilance in Epileptic Patients: A Deep Insight into Phenytoin Behaviour

Abstract

Despite the introduction of new and more expensive anticonvulsant drugs, phenytoin (PHT) is still a first-line medication for common types of epilepsy such as tonic-clonic and complex partial seizures but not for absence seizures. PHT shows a nonlinear kinetics and a narrow therapeutic range, thus a fine balance must be found between efficacy and toxic effects. Since the free (unbound) drug is responsible for producing the pharmacological effect, the concentration in a novel biological fluid more closely related to arterial free plasma drug concentrationsaliva-is used in this study as part of the monitoring strategy. Therefore, in order to optimize therapy in epileptic patients under PHT treatment, plasma and saliva concentrations of PHT were measured, and adverse drug reactions were registered during a 2-year follow-up. CYP2C9, CYP2C19, and epoxide hydrolase polymorphisms (enzymes involved in PHT metabolism) were also analyzed using, in this way, pharmacogenetics for drug safety. The two PHT brands commercially available in our country and used in this study demonstrated similar pattern of efficacy and safety.

Phenytoin-associated movement disorder

“…Common side effects related to PHT are fatigue, allergic reactions in the form of rashes, gastrointestinal symptoms, hirsutism, coarsening of the facies, and gingival hyperplasia. There is a black box warning about the cardiovascular risk associated with rapid infusion rates of this antiepileptic drug[ 9 ]. In this context, abnormal involuntary movements related to PHT such as ataxia and tremor are frequently seen in clinical practice.…”

Status Epilepticus in Post-Transplantation Hyperammonemia Involves Careful Metabolic Management

“…The term status epilepticus (SE) describes the brain’s state when in persistent seizure. SE is a life-threatening condition with a very high mortality rate (estimated at 7.6% to 43%), especially when early identification and treatment is not performed in a timely manner [ 2 ]. SE has a wide variety of known causes; however, metabolic abnormality, especially hyperammonemia, is a rare etiology.…”

“…Elevated serum ammonia is a well-known cause of status epilepticus because ammonia easily crosses the blood–brain barrier and may conjugate with α-ketoglutarate to form glutamate. This leads to brain damage and the precipitation of seizures given the excitatory activity of glutamate in the synaptic membrane [ 2 ]. The phenomenon of hyperammonemia in immunosuppressed post-transplant patients is not well-understood; however, more recently, several studies have detailed a relationship between hyperammonemia and Ureaplasma infection in immunosuppressed patients, including patients with lung transplantation [ 3 , 4 ].…”