Significant Pregabalin Toxicity Managed with Supportive Care Alone

Wood, David M.; Berry, David J.; Glover, Guy; Eastwood, Jane

doi:10.1007/s13181-010-0052-3

Cited by 37 publications

(29 citation statements)

References 8 publications

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“…Pregabalin is not metabolized being cleared entirely by renal excretion with a serum elimination half-life of 5-7 hours in adults. There are reports of significant toxicity in a case of self-poisoning with pregabalin alone 149 ; also, a case of toxicity associated with therapeutic use in a patient with renal failure although the peak drug concentration (predialysis) in this case was only 13 mg/L. 103 The precise role for TDM of pregabalin has not yet been established, although there may be a requirement in patients with renal impairment, to ascertain compliance, where malabsorption is suspected and in cases of suspected overdose.…”

Section: Pharmacokinetic Characteristicsmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

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Section: Pharmacokinetic Characteristicsmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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“…A subsequent case report described the development of complete but transient atrioventricular block following pregabalin overdose 104. However, a review of 42 cases of pregabalin overdose indicates that serious complications are unusual,105 and a case report has described full recovery with general supportive care only, after ingestion of 8.4 grams of pregabalin, which resulted in a serum level of 66.5 mg/L 106…”

Section: Tolerability and Safety Of Pregabalinmentioning

confidence: 99%

Pregabalin for the treatment of generalized anxiety disorder: an update

Baldwin¹,

Ajel²,

Masdrakis³

et al. 2013

NDT

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A previous review summarized what was then known about the potential role of pregabalin in the treatment of patients with generalized anxiety disorder (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in “over-excited” presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD.

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“…Our patient's serum concentration is among the highest reported. A previous case report identified a concentration of 66.5 mcg/mL (three hours post-ingestion of pregabalin 8.4 g) [7]. A separate report identified a concentration of 29 mcg/mL (9 hours post-ingestion of an unknown quantity of pregabalin) [8].…”

mentioning

confidence: 99%

Pregabalin and paradoxical reaction of seizures in a large overdose

Slocum

Schult

Gorodetsky

et al. 2018

Toxicology Communications

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We report the case of a 54-year-old female with intentional pregabalin 3825 mg ingestion that resulted in a rare adverse effect of a witnessed seizure with confirmatory serum concentrations. After presenting alert to the emergency department she became obtunded, only responding to sternal rub (four hours after ingestion). Laboratory evaluation and toxicology panel were unremarkable. Approximately eight hours after the ingestion she had physician-witnessed tonicclonic seizure activity with right gaze deviation for 90 seconds. This is only the third documented case of paradoxical seizure due to a large overdose of pregabalin. Also, the serum concentration observed is among the highest recorded (58 mcg/mL five hours post-ingestion). Pregabalin abuse has been emerging. Clinical toxicologists should be aware of the potential of pregabalin-induced seizures following overdose.

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Significant Pregabalin Toxicity Managed with Supportive Care Alone

Cited by 37 publications

References 8 publications

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Pregabalin for the treatment of generalized anxiety disorder: an update

Pregabalin and paradoxical reaction of seizures in a large overdose

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